Mental Health Pharmacology Nursing CE Course for RNs and LPNs

ed. A collective effort from the child and their support system—including their caregivers, teachers, and therapist—will best assist them in reaching their maximum potential. Behavioral management can be as effective as medication when appropriate caregiver training is provided. Pharmacological treatment should only be considered if behavioral therapy is ineffective or does not provide significant improvement, and there is a moderate-to-severe continued disturbance in the 4- to 5-year-old child’s functioning. The guidelines encourage providers to weigh the risks of prescribing medication before age 6 against the harm of delaying treatment. The AAP 2019 guidelines do not address children with comorbid issues, but these are common in children with ADHD (anxiety, depression substance use disorder [SUD], tic disorders [TD], epilepsy, learning disabilities [LD], oppositional defiant disorder [ODD], sleep disorders, autism spectrum disorders [ASD]) (Chan, 2026a; Lalonde et al., 2025; Solanto, 2025; Wolraich et al., 2019).

For children over 6 years, behavioral therapy with medications can be an effective treatment model for ADHD. When treating a young child with medication, providers must use only agents approved by the US Food and Drug Administration (FDA) for ADHD and avoid off-label use until children reach adulthood (Wolraich et al., 2019). The Centers for Disease Control and Prevention (CDC, 2024b) reports that pharmacotherapy is used to treat ADHD in over 53% of children. The highest rate is among those ages 6–11, and males and females are at similar rates overall (CDC, 2024b; 54.2% vs. 52.6%). The AAP encourages providers to consider delaying pharmacological treatment until the school-aged years, ideally between ages 6 and 11. Even if medication management is initiated, behavioral therapy should remain a part of the treatment plan in this age group. Caregivers should learn the behavioral therapy components to use at home, and teachers should model and implement them during school hours. Once a child reaches adolescence, medications are often used, but behavioral therapy may still be a helpful adjunct. Medications should be started at the lowest possible dose and titrated as needed until the child reaches the maximum benefit while avoiding significant adverse effects. If the child has a “medication vacation” and does not take their medicine for a period, such as during a school break, the dose should be reduced when the medication is restarted and titrated back up slowly (Chan, 2026a; Peterson et al., 2024; Wolraich et al., 2019).

Elementary and middle school-aged children (6-12) should receive treatment with PTBM, behavioral classroom intervention, and medication. Educational interventions and individualized instructional support should be provided within the school environment, through classroom placement, and as additional components of the treatment plan, often including an individualized education program (IEP) or a rehabilitation plan. Adolescents (ages 12-18) should receive FDA-approved medications with their consent, preferably alongside the same behavioral and educational interventions outlined above. Medications are also commonly used during adulthood, as up to one-third of children with ADHD continue to have symptoms into adulthood. There is no cure for ADHD; therefore, medication use aims to lessen hyperactivity and impulsivity symptoms and improve the patient’s ability to concentrate, focus, work, and learn (CDC, 2024a; CHADD, n.d.-c; Chan, 2026a; Peterson et al., 2024; Wolraich et al., 2019).

The pathophysiology of ADHD is not entirely clear but is premised on a complex neurobiological basis involving multiple brain pathways. Functional and structural differences have been noted in the prefrontal cortex, caudate nucleus, basal ganglia, anterior cingulate cortex, and cerebellum regions of the brain in patients with ADHD. Neurotransmitters are endogenous chemical messengers in the brain that transmit signals necessary for normal functioning, and they are thought to play a role in ADHD. Dopamine and norepinephrine are the main neurotransmitters implicated in ADHD disorders, and a deficiency in these vital chemical messengers may be linked to the development of ADHD symptoms. Other neurotransmitters with less extensive influence include serotonin, glutamate, and gamma-aminobutyric acid (GABA). Dopamine influences movement, attention, and motivation; norepinephrine plays a role in maintaining mental activity, regulating mood and excitability, problem-solving, and memory; and serotonin influences mood, sleep, memory, and social behavior. Therefore, medications targeting these neurotransmitters are considered the mainstay of pharmacological treatment (da Silva et al., 2023; Noah & Sedky, 2025; Tarraza, 2023).

Two classes of medications are commonly prescribed for treating ADHD: stimulants and non-stimulants. These medications primarily work by blocking the reuptake of dopamine and norepinephrine, thereby increasing their release and improving cognition and attention. Stimulants are the most widely used and well-known class of medications for managing ADHD-related symptoms and have been shown to reduce symptoms by 70%–80% of children with ADHD. Non-stimulants were approved for the treatment of ADHD in 2003, and their effects can last longer, up to 24 hours, but are slower to take effect. Stimulants include amphetamines and methylphenidates, and they are available in immediate-release (IR), sustained- or extended-release (SR, ER, XR), and long-acting (LA) formulations. Longer-acting ER stimulants are associated with improved compliance with treatment, as they are only dosed once a day instead of the 2–3 times per day (BID or TID) required with IR formulations (CDC, 2024a; Chan, 2026a; NIMH, 2023b; Noah & Sedky, 2025; Wolraich et al., 2019).

Stimulants

The most common medications used to treat ADHD are stimulants. Most children (70%-80%) diagnosed with ADHD and medicated with a stimulant exhibit significantly improved ADHD-associated behavior (CHADD, n.d.-b; Efron & Coscini, 2025). Stimulants are all categorized by the US Drug Enforcement Administration (DEA) as Schedule II with boxed warnings for high abuse, misuse, and addiction potential, and previously by the FDA as pregnancy Category C (i.e., risk cannot be ruled out). These medications were first administered to children with behavioral and learning disorders in 1937. Hundreds of controlled studies have been conducted (involving more than 6,000 children, adolescents, and adults) to determine the short-term effects of these medications. There are no long-term studies (i.e., more than a few years) on the effects of these medications, as this research would necessitate withholding treatment over many years for patients with significant impairment, which has been deemed unethical. However, individuals have used these medications for many years without serious adverse effects. Stimulants (methylphenidate, amphetamines) reduce hyperactivity by increasing dopamine levels in the brain. The most common stimulants used for ADHD are methylphenidate (Ritalin, Concerta, Aptensio, Jornay PM), dextroamphetamine (Dexedrine), and dextroamphetamine/amphetamine (Adderall). They are available as IR formulas (lasting about 4 hours), LA formulas (ranging from 6 to 12 hours), and ER preparations (lasting up to 24 hours). Many caregivers and patients prefer LA or ER formulations, as these may reduce the “ups and downs” experienced throughout the day and eliminate the need to dose medication at school or work (CHADD, n.d.-a, n.d.-b; Chan, 2026c; FDA, 2023; Hasan et al., 2026; Wolraich et al., 2019).

Amphetamines induce CNS activity, activating the acute stress response (fight or flight) and producing a paradoxical calming effect. CNS activation triggers physiological changes that mimic stress or threat. Amphetamines stimulate the release of adrenaline and raise cortisol and other stress hormone levels, causing increased heart rate and blood pressure. As a result, blood flow is redirected to the muscles and away from the brain. In small doses, amphetamines can alleviate tiredness and help patients feel alert and refreshed (Wolraich et al., 2019; Woods, 2023).

Dextroamphetamine/amphetamine (Adderall) is considered one of the first-line pharmacological treatments for ADHD and is widely used in individuals 6 years and older. Initial dosing for patients 6 and older is 5 mg (IR tabs) by mouth once or twice daily. With ER tabs, the initial dose for children ages 6–12 is 5–10 mg by mouth once daily in the morning, with the dose increased. For adolescents ages 13–17, the initial dosing is 10 mg by mouth daily in the morning. The adult dose is 20 mg daily in the morning. Dextroamphetamine/amphetamine (Adderall) can be administered with or without food but should be taken in the morning to avoid insomnia. Patients taking the ER formulation should swallow capsules whole, or the contents can be sprinkled on a bite of food that does not require chewing (applesauce or pudding) (UpToDate Lexidrug, n.d.-a; Wolraich et al., 2019; Woods, 2023).

Dextroamphetamine (Dexedrine) is similar to dextroamphetamine/amphetamine (Adderall) but without pure amphetamine. Dextroamphetamine (Dexedrine) should not be administered in the late evening due to the risk of insomnia. This medication interacts with antihypertensives (diminishes effects), monoamine oxidase inhibitors (MAOIs; may cause severe hypertension), and acidic foods or fruit juices due to delayed absorption and decreased effectiveness. It should be used cautiously in patients experiencing agitation, motor or phonic tics, or Tourette syndrome (UpToDate Lexidrug, n.d.-b; Woods, 2023).

Lisdexamfetamine (Vyvanse) is an LA preparation and differs from other medications in this class due to its pharmacokinetics. It is considered a prodrug, which means it must undergo chemical conversion by metabolic processes before becoming an active agent. It does not convert to its active formulation until it reaches the gastrointestinal (GI) tract; therefore, its effects take 60–90 minutes. The drug has less misuse potential than dextroamphetamine/amphetamine (Adderall), as it cannot be absorbed intravenously or transmucosally. For adults and children ages 6–17, the initial dose is 30 mg orally once daily in the morning. Lisdexamfetamine (Vyvanse) should be taken in the morning with or without food to prevent insomnia (UpToDate Lexidrug, n.d.-c; Wolraich et al., 2019; Woods, 2023).

Methylphenidate (Ritalin, Ritalin LA, Concerta, Aptensio XR, Jornay PM, Daytrana) stimulates the release of terminal norepinephrine stores, promoting nerve impulse transmission. At high doses, the effects are mediated by dopamine. The most common formulation is oral methylphenidate (Ritalin, Concerta, Aptensio XR, Jornay PM), but it is also available as a transdermal patch (Daytrana). Chewable tablets must be taken with at least 240 mL of water. IR formulations should be administered in divided doses throughout the day, at least 30–45 minutes before meals and no later than 6 p.m., due to the risk of insomnia. The exception is methylphenidate (Jornay PM), which should be administered between 6:30 and 9:30 p.m. If using methylphenidate (Daytrana), the patch should not be placed along the waistline or in an area where tight clothing could pull it away from the skin. When changing patches, the site should be moved to the alternate side of the body (UpToDate Lexidrug, n.d.-d; Woods, 2023).

The adverse effects of stimulants include hypertension, tachycardia, anxiety, decreased appetite, sleep problems, personality changes, tics, stomach pain, and headaches. Less commonly reported adverse effects include allergic reactions, fever, arthralgia, psychosis, and depression. Sudden death is a rare adverse effect in patients with preexisting cardiac conditions. The nurse should counsel patients on strategies to manage insomnia, including taking the medication before noon unless otherwise advised, limiting or avoiding caffeine, and maintaining healthy sleep hygiene. When insomnia requires pharmacological management, melatonin is recommended as the initial intervention because it occurs naturally in the body and is nonaddictive. Some patients may require adjunctive prescription sleep aids (clonidine [Catapres, Kapvay] or trazodone [Desyrel]), which are used in children and adults. Medications such as eszopiclone (Lunesta) and zolpidem (Ambien) should be prescribed only for adults and taken 30–60 minutes before bedtime (Chan, 2026c; NIMH, 2023b; Tarraza, 2023; Woods, 2023).

Stimulants carry a risk for diversion (i.e., when legitimate stimulant prescriptions for ADHD are given or sold to those who are not prescribed the medication for personal use or reasons other than treating ADHD). When taken at doses and via routes other than those prescribed, stimulants can increase dopamine levels in the brain in a rapid and highly amplified manner, similar to other drugs commonly misused, such as opioids, thereby disrupting communication between brain cells and producing euphoria. As a result, these biochemical processes and subsequent euphoric effects increase the risk of addiction. Some people describe a stimulant rebound during the period between dosing as the medication is wearing off, in which they can experience a negative mood, fatigue, or hyperactivity. These symptoms can be managed by adjusting the dose or schedule of IR formulas or by switching to an LA formula, if possible (CHADD, n.d.-b, n.d.-c; Forrest et al., 2025; Wolraich et al., 2019).

Non-Stimulants

Non-stimulants are also highly effective in reducing ADHD symptoms but generally take longer to start working. Non-stimulants are often used instead of stimulants in patients with unacceptable adverse effects or inadequate results, or as an adjunct with stimulants to enhance effects. Non-stimulants can help improve focus and attention and decrease impulsivity. Some of the most common non-stimulant medications include clonidine (Catapres, Kapvay), guanfacine ER (Intuniv), atomoxetine (Strattera), and viloxazine (Qelbree). Alpha-2 adrenergic agonist antihypertensives clonidine (Catapres, Kapvay) and guanfacine (Tenex, Intuniv) have been approved for ADHD symptoms in children (hyperactivity, aggression). Due to their efficacy and low adverse-effects profile, they are the preferred nonstimulant treatment for children ages four and up, including those with comorbid conditions. Clonidine (Catapres, Kapvay) and guanfacine (Tenex, Intuniv) are believed to work by affecting the available levels of norepinephrine and dopamine. Only the ER form of guanfacine (Intuniv) is approved to treat ADHD. These drugs risk significant adverse effects (hypotension, sedation, hypertensive rebound). Another treatment option that has been explored for adult ADHD patients is modafinil (Provigil), a wake-promoting agent that the FDA currently approves for narcolepsy and extreme fatigue in patients with primary sleep disorders. However, due to safety concerns and insufficient research evidence, it is not considered a treatment option (Chan, 2026b; CHADD, n.d.-b; Martins et al., 2024; Nazarova et al., 2022; UpToDate Lexidrug, n.d.-e; Wolraich et al., 2019; Woods, 2023).

Atomoxetine (Strattera) and viloxazine (Qelbree) are FDA-approved oral selective norepinephrine reuptake inhibitors (SNRIs) that alleviate inattention and hyperactivity symptoms of ADHD by selectively inhibiting norepinephrine reuptake. They are not controlled substances and thus determined to have low misuse potential. They have a slower onset, taking 4–6 weeks to take full effect. Adverse effects include headaches, insomnia, dizziness, irritability, fatigue, abnormal dreams, sleep disorder, anxiety, orthostatic hypotension, tachycardia, palpitations, hot flashes, abdominal pain, constipation, dyspepsia, nausea, vomiting, anorexia, urinary retention, and ejaculatory problems (Chan, 2026b; NIMH, 2024b; Noah & Sedky, 2025; Wolraich et al., 2019; Woods, 2023).

Other antidepressants that target the neurotransmitter norepinephrine are sometimes used to treat ADHD, but they are not FDA-approved for this indication and are thus considered off-label. Venlafaxine (Effexor) inhibits the reuptake of norepinephrine, serotonin, and dopamine. Bupropion (Wellbutrin) is a norepinephrine and dopamine reuptake inhibitor (NDRI) that helps improve concentration and focus and reduces hyperactivity. Since it does not influence serotonin, it differs from many other antidepressants. Possible adverse effects of bupropion (Wellbutrin) include anxiety, agitation, increased motor activity, insomnia, tremors or tics, dry mouth, headaches, nausea, and an increased risk for seizures in susceptible individuals or those with a history of eating disorders. Less commonly, duloxetine (Cymbalta) may be used; it works by blocking the reuptake of norepinephrine and serotonin. Like atomoxetine (Strattera) and viloxazine (Qelbree), these drugs are not controlled substances and have low misuse potential but should be used with caution; extensive patient counseling regarding the possible adverse effects and risks is recommended. They are not recommended for children with depression and should be used cautiously in adolescents due to the increased risk of suicide accompanying antidepressant use (Chan, 2026b; CHADD, n.d.-b; WHO, 2025b).

In June 2020, the FDA approved EndeavorRx, a new treatment option for ADHD in children. EndeavorRx is presented as an immersive video game played on a mobile device, available by prescription and approved for children ages 8–12. The game is considered a medical device designed to be used with other therapies and should not be used as monotherapy. EndeavorRx uses sensory stimuli and motor challenges to engage brain regions involved in attention. Recent research has shown statistically significant benefits in children, adolescents, and adults with ADHD. However, this has not become a generalized, recommended therapy due to concerns regarding the adverse effects of increased screen time (Akili Interactive Labs, n.d.-a, n.d.-b; Chan, 2026a; Richmond, 2024; Stomatis et al., 2024). For more information on ADHD, refer to the NursingCE course Attention Deficit Hyperactivity Disorder.

 

Depression

According to the WHO, as much as 4% of the global population is affected by depression (approximately 332 million people), including 5.7% of adults and 5.9% of adults over 70. In the United States, an estimated 21 million adults (8.3%) experience at least one major depressive episode (MDE) per year. The prevalence is highest among individuals ages 18–25 (18.6%), and females are affected more frequently than males (10.3% vs. 6.2%). In 2024, approximately 3.8 million (15.4%) adolescents aged 12–17 in the United States experienced at least one MDE the previous year. Despite the prevalence of depression, only one-third of people with depressive disorders in high-income countries received mental health treatment. In the United States, only 61% of adults aged 18 and older and 40.6% of adolescents who experienced an MDE in 2021 received medical treatment that same year. Severe depression, when treated or untreated, can lead to suicide (NIMH, 2023a; Substance Abuse and Mental Health Services Administration, 2025; WHO, 2025a).

The DSM-5-TR states that all forms of depressive disorders include a sad, empty, or irritable mood alongside somatic and cognitive changes that significantly impact the patient’s functional capacity. Depression can occur in children and adolescents, but is most common in adults and often presents as irritability or anxiety in children. Their major distinctions are limited to symptom duration, timing, or presumed etiology (APA, 2022; NIMH, 2024d). There are different classifications of depression, including:

• persistent depressive disorder (PDD), or dysthymia, lasts at least 2 years in adults and 1 year in children
• substance/medication-induced depressive disorder: depression-like phenomena caused by substance misuse, abuse of prescription medications (opioids), or illicit drug use
• disruptive mood dysregulation disorder: characterized by temper outbursts that occur 3 times per week for at least 1 year
• premenstrual dysphoric disorder: hormone-induced depression that occurs the week before menstruation
• depression with peripartum onset: characterized by symptoms of depression that make it difficult to care for oneself and the baby (or other children)
• depression with psychosis: characterized by an MDE combined with concurrent psychotic symptoms, including delusions or hallucinations
• seasonal affective disorder (SAD): depression that has an onset during the winter months when there is less natural sunlight and is accompanied by increased sleep, weight gain, and social withdrawal
• bipolar disorder: a separate mood disorder with episodes of extremely low mood that meets the criteria for major depression, but which includes periods of depression (APA, 2022; Avery, 2024; NIMH, 2024d)

The exact cause of depression is unknown and is likely due to a combination of risk factors. While depression is a psychological disorder, several contributing influences include environmental, genetic, and psychological or biochemical elements. Different chemicals in the brain can contribute to depressive symptoms and are the focus of pharmacological treatments. A previously accepted theory that depression stems from a chemical imbalance in the monoamines in the brain of serotonin, norepinephrine, and dopamine has shifted over the last 15–20 years. Theories regarding alterations in brain architecture and complex circuitry have led researchers to question whether these neurotransmitters are not simply a messenger of information or a symptom of depression as opposed to the cause itself. Advances in genetics and functional neuroimaging have opened new and exciting avenues for investigation and altered how depression is viewed over the last 20 years, leading to changes in treatment options (APA, 2024, 2022; Krishnan, 2026).

An individualized treatment plan should be developed using shared decision-making and will vary based on the severity of the patient’s depression (mild, moderate, moderate-severe, or severe). Treatment for depression may include counseling, therapy, and/or medication. Adequate treatment can prevent suicide related to depression. The most effective treatment for depression is a combination of psychotherapy with pharmacological treatment, such as antidepressant medication (NIMH, 2024d; Rush, 2025a).

Psychotherapy is a successful, beneficial, and cost-effective treatment for depression. The APA (2022) defines psychotherapy as any psychological service delivered by a trained professional (i.e., psychotherapist) that employs principles of communication and interaction to assess, diagnose, and treat mental health disorders. Also referred to as talk therapy, psychotherapy is premised on establishing a supportive environment and collaborative relationship between a patient and a psychotherapist to foster open discussion in an objective, neutral, and nonjudgmental manner. A psychotherapist is any individual who is professionally trained and licensed by their respective state licensing boards to treat mental health conditions (psychologist, psychiatrist, psychiatric nurse, APRN, counselor, therapist, or social worker). Research demonstrates that depressed individuals who receive both virtual and in-person psychotherapy achieve more durable treatment responses (i.e., are less prone to relapse) and better symptom control than when medication is used alone (Rush, 2025a; Zandieh et al., 2024).

While there are several types of psychotherapy, the most effective options for depression include cognitive-behavioral therapy (CBT), short-term dynamic psychotherapy, mindfulness-based cognitive therapy (MBCT), family and/or couples therapy, problem-solving therapy (PST), behavioral activation (BA), supportive psychotherapy, and interpersonal therapy (IPT). Technological advances in therapy include internet-based psychotherapy (IBP), artificial intelligence (AI)-based tools, and digital health interventions (DHIs), which are self- or clinician-guided adjunctive nonpharmacological therapies. AI-assisted psychotherapy has shown promising initial results in decreasing depression, anxiety, and eating disorders. Its widespread therapeutic use is limited, however, by questions regarding risks, including safety, increased loneliness, or emotional overdependence. Further research is needed to establish safety prior to clinical adoption. DHIs (Spark Direct, MoodGYM, Pacifica/Sanvello, Deprexis, Good Days Ahead, Rejoyn) are online or app-based CBT-centered programs that have shown promising results in randomized controlled studies for the treatment of mild MDD. Rejoyn was the first to be approved by the FDA in 2024 for adjunct treatment of MDD. Currently, Spark Direct, Deprexis, and Rejoyn are FDA-approved. Each patient and psychotherapist is encouraged to set mutually agreed upon and realistic goals that are periodically reevaluated. Patient response varies based on the presenting issue, its severity and complexity, interference with functioning, openness to treatment, and the specific interventions. If the patient does not improve within the planned treatment duration, the intervention should be reassessed, and other therapeutic strategies considered. There is no universally effective approach to treating depression. Experienced psychotherapists typically blend modalities and tailor the treatment to meet each patient’s needs, often altering the treatment course when underlying issues are revealed as the patient progresses through therapy (APA, 2019; Lam et al., 2024; Ophir & Rosenberg, 2026; Phan et al., 2023; Richmond, 2024; Rush, 2025a, 2025c; Wampold, 2019; Zandieh et al., 2024).

While mild-to-moderate depression can be effectively treated with psychotherapy alone, moderate-to-severe cases of depression often require the addition of medication. It is important to note that numerous complementary and alternative treatments can be used as an adjunct to other evidence-based treatments for depression (exercise and yoga, light therapy, acupuncture, mindfulness training). When combined with evidence-based treatments (prescription medications, psychotherapy), these interventions can contribute to the overall treatment plan for depression (National Center for Complementary and Integrative Health [NCCIH], 2021; Rush, 2025a, 2025c).

There are over-the-counter (OTC) pharmacological agents available for the management of depression (Hypericum perforatum [St. John's wort], omega-3 fatty acids [fish oil], S-adenosyl methionine [SAM-e]). However, these agents are not FDA-approved for depression, nor are they FDA-regulated to ensure their safety and efficacy. The lack of FDA oversight and regulation of these agents raises concerns about the consistency of formulations, the purity of ingredients, and their safety profiles. Although patients do not require a prescription to obtain these drugs, they still pose a risk of significant adverse effects and dangerous drug interactions. Hypericum perforatum (St. John’s wort) is notorious for interacting with several prescription drugs, either expediting or diminishing the metabolism of the prescribed agent, leading to reduced efficacy or higher toxicity. For example, patients should be warned never to take hypericum perforatum (St. John’s wort) with a prescribed antidepressant, as the combination leads to increased levels of serotonin in the body, which can cause mild to severe effects. For this reason, as well as the lack of clarity regarding optimal dosing, St. John’s wort is not recommended for depression management. Studies have shown that adding a folate supplement, such as l-methylfolate (Denovo), can enhance the effectiveness of antidepressant medications without causing dangerous drug interactions. Furthermore, some studies have demonstrated that l-methylfolate (Denovo) supplementation may be an effective adjunctive therapy or a stand-alone treatment for reducing depressive symptoms and improving cognitive function. SAM-e lacks high-quality evidence that it is beneficial in depression treatment, but may be helpful as an adjunctive treatment. Similarly, omega-3 fatty acids may be a helpful add-on treatment (Gitlin, 2025; NCCIH, 2021).

In patients with moderate-to-severe depression, antidepressant medications are the pharmacological treatment of choice. Medication therapy aims to help reduce or control the symptoms of depression. The bulk of medications currently FDA-approved for treating depression target the three neurotransmitters historically associated with depression: serotonin, norepinephrine, and dopamine. Due to their adverse-effects profiles, most antidepressants should be initiated at a low dose, tapered up slowly, and tapered down before discontinuing. If they are stopped abruptly, withdrawal symptoms (dizziness, headaches, flu-like syndrome [tiredness, chills, muscle aches], agitation, irritability, insomnia, nightmares, diarrhea, nausea) may ensue. Discontinuation can also lead to the return of depressive symptoms. Regardless of the medication prescribed, patients must be counseled that antidepressants may take at least 2–4 weeks to have an effect and 12 weeks to achieve full benefits. Disturbances in sleep, appetite, and concentration often improve before a notable change in mood. While mild-to-moderate depression can often be treated with therapy alone, moderate-to-severe cases of depression often require the addition of medication. Females of childbearing age should be advised that most antidepressants were previously categorized by the FDA as pregnancy category C (risk cannot be ruled out) except for paroxetine (Paxil; category D) and bupropion (Wellbutrin; category B), with slight variations between the medications’ safety for those who are lactating (NIMH, 2023b, 2024d; Rush, 2025a; Sheffler et al., 2023).

In 2004, the FDA required a boxed warning to be printed on the labels of all antidepressant medications regarding the risk of increased suicidality among children and adolescents taking these medications. The warning was expanded in 2007 to include all young adults, especially those under 25, stating that these individuals may experience increased suicidal thoughts or behaviors during the first few weeks of taking an antidepressant. Before starting medication therapy, the individual may have been too paralyzed by depression to make a suicide plan. Therefore, the risk of suicide rises as symptoms begin to improve on antidepressant therapy. An increase in suicidal thoughts has also been documented in patients taking antidepressants for other conditions or indications. As antidepressants became more commonly prescribed for anxiety and other mental health conditions, reports of patients’ suicidal thoughts and actions became more worrisome to providers and family members. If a depressed person who is taking antidepressants becomes suicidal, it is always a cause for concern. However, if someone not previously depressed and taking antidepressants for another indication becomes suicidal, it raises additional questions about these medications’ safety. Researchers found evidence that individuals taking antidepressant medication may have an even higher risk of suicide than individuals whose depression improves for other reasons. The FDA also requires manufacturers of antidepressants to provide a Patient Medication Guide (MedGuide) to distribute to patients, advising them of precautions to reduce the risk of suicide. Healthcare professionals (HCPs) should ask patients, especially young persons, about suicidal thoughts before prescribing antidepressants (Ault, 2024; Moreland & Bonin, 2024; Naveed et al., 2021). Table 1 lists the points that must be included in the boxed warning.

Table 1

FDA Antidepressants Boxed Warning Points

Antidepressants increase the risk of suicidal thinking and behavior (suicidality) for children and adolescents with MDD and other psychiatric disorders.

Anyone considering an antidepressant for a child or adolescent for any clinical indication must balance the risk of increased suicidality with the clinical need.

Patients who are started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior.

Families and caregivers should be advised to observe the patient closely and communicate with the prescriber.

A statement must be made regarding whether the prescribed drug is approved for any pediatric indication(s) and, if so, which one(s).

(Moreland & Bonin, 2024)

The current evidence does not recommend one prescribed agent over another for the treatment of depression. However, selective serotonin reuptake inhibitors (SSRIs) are typically cited as the safest initial choice that causes the fewest adverse effects, followed by SNRIs. As a drug class, the most common adverse effects of antidepressants include nausea, weight gain, diarrhea, sleepiness, and sexual dysfunction (i.e., loss of libido or impotence; Coryell, 2026b; NIMH, 2023b).

SSRIs and SNRIs

SSRIs selectively block serotonin reuptake, increasing the amount of serotonin available in the brain. Commonly prescribed SSRIs include citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), and venlafaxine (Effexor). Prozac (fluoxetine) and escitalopram (Lexapro) are the only antidepressants that are FDA-approved for use in children with depression. Common adverse effects of SSRIs include nausea, vomiting, diarrhea, headaches, dry mouth, drowsiness, insomnia, nervousness, agitation, restlessness, QTc prolongation, orthostatic hypotension, sexual dysfunction, and appetite changes leading to weight loss or weight gain. Less common adverse effects include hyponatremia, abnormal bleeding or bruising, and declining bone mineral density (Coryell, 2026b; UpToDate Lexidrug, n.d.-f; Rush, 2025b; Woods, 2023; Zhong et al., 2025).

SNRIs include duloxetine (Cymbalta), venlafaxine (Effexor), desvenlafaxine (Pristiq), milnacipran (Savella), and levomilnacipran (Fetzima). Adverse effects include nausea, headaches, dizziness, excessive sweating, tiredness, constipation, insomnia, sexual dysfunction, and anorexia (Coryell, 2026b; Rush, 2025b; UpToDate Lexidrug, n.d.-g; Woods, 2023; Zhong et al., 2025).

SSRIs and SNRIs can increase serotonin levels in the body, posing a risk for serotonin syndrome. Serotonin syndrome is characterized by agitation, anxiety, confusion, a high fever, sweating, tremors, a lack of coordination, dangerous fluctuations in blood pressure, and a rapid heart rate. Patients must seek immediate medical attention because this is a potentially life-threatening condition. Furthermore, SSRIs and SNRIs increase suicide risk and withdrawal symptoms if stopped abruptly. These medications should not be used within 14 days of an MAOI (Boyer, 2024; Coryell, 2026b; Woods, 2023).

Tricyclic Antidepressants and Tetracyclic Antidepressants

Tricyclic antidepressants (TCAs) and tetracyclic antidepressants are an older class of medications that include nortriptyline (Pamelor), imipramine (Tofranil), amitriptyline (Elavil), and desipramine (Norpramin). TCAs inhibit norepinephrine and serotonin reuptake but with significantly more adverse effects (sedation, increased appetite, weight gain, dry mouth, constipation, hypotension, lightheadedness, drowsiness, blurred vision, tremors, excessive sweating, sexual dysfunction). Less common but serious adverse effects include life-threatening irregular heart rate, urinary retention, and seizures. TCAs also carry a risk for serotonin syndrome, suicide risk, and withdrawal symptoms if discontinued abruptly. These medications should also be avoided within 14 days of MAOI use (Hirsch & Birnbaum, 2025c; Moraczewski et al., 2023; Woods, 2023).

 

Monoamine Oxidase Inhibitors 

MAOIs were the first type of antidepressant developed. They impair serotonin metabolism and block monoamine oxidase, an enzyme that breaks down excess tyramine in the body. Tyramine is an amino acid that helps regulate blood pressure and is found naturally in the body and certain foods. MAOIs available in the United States include tranylcypromine (Parnate), phenelzine (Nardil), isocarboxazid (Marplan), and selegiline (Emsam) in a transdermal skin patch. Due to the risk of serious adverse effects, the use of MAOIs for treating depression is reserved for patients who have failed all other treatment options. MAOIs have dangerous drug and food interactions; HCPs must warn patients to avoid foods containing high levels of tyramine (aged cheese [aged cheddar, Swiss, parmesan, blue cheeses]; cured, smoked, or processed meats [pepperoni, salami, hotdogs, bologna, bacon, corned beef, smoked fish]; pickled or fermented foods [sauerkraut, kimchi, tofu]; sauces [soy sauce, miso, and teriyaki sauce]; soybean products; alcoholic beverages [beer, red wine, liquors]). Other adverse effects of MAOIs include dry mouth, nausea, diarrhea or constipation, headaches, drowsiness, insomnia, dizziness, lightheadedness, hypotension, loss of libido, weight gain, urinary retention, involuntary muscle jerks, muscle cramps, and paresthesia. MAOIs are associated with increased suicidality and withdrawal symptoms if stopped abruptly. Before prescribing MAOIs, HCPs must ensure all other antidepressants have been discontinued for at least 14 days due to the heightened risk of serotonin syndrome. Patients should also be counseled to avoid OTC decongestants and other cold medications due to the heightened risk for dangerous hypertensive crises (Coryell, 2026b; Hirsch & Birnbaum, 2025a; Patel & Saadabadi, 2025; Woods, 2023). Table 2 outlines the dosing and patient information for various classes of antidepressants.

Table 2

Antidepressants by Medication Class

   

Drug Class

SSRIs

Drug

Citalopram (Celexa)

Escitalopram (Lexapro)

Fluoxetine (Prozac)

Fluvoxamine (Luvox)

Paroxetine (Paxil)

Sertraline (Zoloft)

Adverse Effects

More likely to cause QTc prolongation and sexual dysfunction

More likely to cause sexual dysfunction; QTc prolongation possible

More likely to cause sexual dysfunction or insomnia/agitation

More likely to cause sexual dysfunction, insomnia/agitation, orthostatic hypotension, GI disturbance, and/or weight gain

More likely to cause sexual dysfunction, orthostatic hypotension, and/or weight gain

More likely to cause sexual dysfunction, GI disturbance, and/or insomnia/agitation

Patient Education

continue therapy even after symptoms improve avoid alcohol females of reproductive age must use contraception be cautious when operating heavy machinery

Drug Class

SNRIs

Drug

Duloxetine (Cymbalta)

Desvenlafaxine (Pristiq)

Levomilnacipran (Fetzima)

Venlafaxine (Effexor)

Adverse Effects

More likely to cause GI disturbance, may cause insomnia

More likely to cause GI disturbance, may cause insomnia

More likely to cause GI disturbance

More likely to cause sexual dysfunction or GI disturbance, may cause insomnia, QTc prolongation, or drowsiness

Patient Education

do not stop therapy abruptly avoid activities that are hazardous or require mental alertness avoid alcohol consumption sexual dysfunction may occur

Drug Class

TCAs and Tetracyclic Antidepressants

Drug

Amitriptyline (Elavil)

Nortriptyline (Pamelor)

Imipramine (Tofranil)

Desipramine (Norpramin)

Doxepin (Silenor)

Adverse Effects

Most likely to cause anticholinergic effects, drowsiness, weight gain, and sexual dysfunction

May cause anticholinergic effects, drowsiness, or QTc prolongation in some

Most likely to cause orthostatic hypotension, weight gain, drowsiness, anticholinergic effects, QTc prolongation, or sexual dysfunction

May cause drowsiness, orthostatic hypotension, or QTc prolongation in some

Most likely to cause drowsiness of all cyclic antidepressants and is associated with weight gain

Patient Education

for higher doses, administer in the late afternoon or evening to prevent daytime sedation when taken at bedtime, morning orthostatic hypotension may occur; change positions slowly when getting out of bed avoid activities that require alertness or psychomotor coordination can combat dry mouth by sucking on hard candies or chewing gum

Drug Class

MAOIs

Drug

Tranylcypromine (Parnate)

Phenelzine (Nardil)

Isocarboxazid (Marplan)

Selegiline (Emsam)

Adverse Effects

Most likely to cause sexual dysfunction, and may cause insomnia/agitation or orthostatic hypotension

Most likely to cause sexual dysfunction and orthostatic hypotension; may cause drowsiness

Most likely to cause sexual dysfunction

May cause anticholinergic effects, insomnia, or orthostatic hypotension

Patient Education

selegiline (Emsam) use may result in a positive urine test for amphetamines apply the patch to dry, intact skin on the upper torso, thigh, or outer arm every 24 hours apply the patch at the same time every day do not cut the patch into smaller pieces avoid alcohol consumption avoid all foods containing tyramine avoid cold and flu medications

(Hirsch & Birnbaum, 2025a, 2025b, 2025c; Nelson, 2026; Rush, 2025b; Woods, 2023)

Uncategorized and Atypical Antidepressants

There are a few uncategorized and atypical antidepressants that have varying mechanisms of action. Bupropion (Wellbutrin) is an atypical antidepressant that inhibits the reuptake of dopamine and norepinephrine. It is prescribed for depression, as well as SAD and smoking cessation. Bupropion (Wellbutrin) is one of the few antidepressants not frequently associated with sexual dysfunction. However, it poses a seizure risk, so it should be avoided in patients with preexisting seizure disorders. It primarily affects dopamine in the brain and therefore does not carry a risk for serotonin syndrome. The most common adverse effects include headaches, weight loss, dry mouth, insomnia (worse with IR formula), nausea, dizziness, constipation, tachycardia, QTc prolongation, and sore throat (FDA, n.d.; Rush, 2025c; Woods, 2023).

Mirtazapine (Remeron) is an atypical tetracyclic antidepressant that antagonizes alpha-2 adrenergic and serotonin receptors. Mirtazapine (Remeron) can cause increased cholesterol and triglyceride levels and should be used cautiously by patients with a personal or family history of heart disease or irregular heart rhythm. Other common adverse effects include increased appetite, weight gain, and dizziness. Rare and severe adverse effects include agranulocytosis (low white blood cells) and angle-closure glaucoma (eye pain, changes in vision, swelling, or redness in or around the eye). Mirtazapine (Remeron) should not be taken within 14 days of an MAOI due to the heightened risk of serotonin syndrome. HCPs should advise patients without insomnia to take the medication at bedtime to avoid daytime drowsiness, especially when performing tasks that require alertness, such as operating heavy machinery (Coryell, 2026b; Hirsch & Birnbaum, 2025c; NAMI, 2024; Woods, 2023).

Trazodone (Desyrel) is an antidepressant that inhibits serotonin transporters and serotonin type 2 receptors. It inhibits the reuptake of serotonin and blocks histamine and alpha-1-adrenergic receptors. It is usually prescribed for depression when other medications have failed. HCPs must ensure that MAOIs are discontinued at least 14 days before initiating trazodone (Desyrel). Because trazodone (Desyrel) causes significant sedation, it may be useful at bedtime for patients with insomnia and depression. Rare adverse effects include priapism (a persistent and painful erection not associated with sexual arousal) and cardiac arrhythmias (Coryell, 2026b; Patel & Saadabadi, 2025; Shin & Saadabadi, 2024).

Brexanolone (Zulresso) is a neuroactive steroid GABA A receptor-positive modulator approved by the FDA in 2019 to treat depression of postpartum onset for individuals older than 15. Due to safety concerns, it was withdrawn from the market in 2025, and a similar oral product, zuranolone (Zurzavae), which was FDA approved in 2023, has taken its place. While the mechanism of action is not fully understood, it is thought to be related to its positive allosteric modulation of GABA A receptors. Zuranolone (Zurzavae) is administered orally, 30 mg/day for 14 days. Common adverse effects include somnolence, headache, and dizziness. Brexanolone (Zulresso) was administered as an infusion over 60 hours. Patients experienced excessive fatigue, tiredness, sedation, or a sudden loss of consciousness during the infusion. It was also associated with an increased risk of suicidality and a risk for misuse. While neurosteroids have shown a statistically significant, rapid improvement in postpartum depressive mood symptoms, further research is needed to clarify best clinical usage, addictive potential, and long-term outcomes (FDA, 2025b; Haris et al., 2025; Sondervan et al., 2025; Woods, 2023).

Resistant Depression

Over half of patients being treated for depression fail to respond to first-line therapy. Resistant depression is the failure of at least two other antidepressants (administered for at least 12 weeks each) without achieving remission or at least a 50% improvement in mood. Often, the resistance is not related to the medication or treatment but to the patient’s compliance with administration. Failure can also be due to an incorrect dose or insufficient time for a therapeutic response to develop. For some patients (those switching from an SSRI to an SNRI or those adding a second medication to the regimen), a change in medication therapy may be warranted. Psychotherapy should be added if not already a component of the treatment plan, and brain-stimulation therapies can be considered (APA, 2022; Pigott et al., 2023; Thase & Connolly, 2025).

 

Esketamine (Spravato)

Esketamine (Spravato) is an N-methyl-d-aspartate (NMDA) antagonist made from ketamine, an anesthetic introduced in the 1960s to treat battle wounds during the Vietnam War. Since then, ketamine has gained attention regarding its role in treating severe depression. In 2019, esketamine (Spravato) nasal spray, a more potent version of ketamine, earned FDA approval when used in conjunction with an oral antidepressant for adults with treatment-resistant depression. Esketamine (Spravato) works by increasing levels of the neurotransmitter glutamate in the brain. It has a rapid onset, immediately impacting brain cells and relieving depressive symptoms within hours. Common adverse effects include dissociation (difficulty with attention, judgment, and thinking), nausea, dizziness, drowsiness, vertigo, and anxiety. It has a boxed warning related to its risk for sedation, dissociation, misuse, dependence, and suicidal thoughts and behaviors. Therefore, it is a federally controlled substance only available through a Risk Evaluation and Mitigation Strategy (REMS) program. Esketamine (Spravato) must be administered under the supervision of an HCP in a health care setting that is certified in the REMS program. Patients cannot take the spray home and must be monitored for signs of sedation and dissociation for at least 2 hours following each dose. The first 1–4 weeks of treatment administration are twice weekly, then once weekly during weeks 5–8. The maintenance dose is administered once weekly or every other week based on patient response. A warning was issued in 2022 by the FDA regarding the risks of pharmacies compounding nasal ketamine formulations to avoid the REMS program (FDA, 2022; NIMH, 2023b; Reif et al., 2023; Woods, 2023). For more information on Depression, refer to the NursingCE course on Depression.

Anxiety

Anxiety disorders are the most common mental health illness in the United States, affecting more than 40 million (19.1%) adults aged 18 and older. It is estimated that 25%-32% of adolescents between the ages of 13 and 18 have an anxiety disorder. Individuals with anxiety are 3–5 times more likely to visit an outpatient provider and are 6 times more likely to be hospitalized for psychiatric treatment. People with anxiety disorders generally experience persistent concern and worry associated with nonspecific physical and psychological symptoms (restlessness, sleep disturbances, irritability, fatigue, difficulty concentrating, or muscle tension) that impact their life negatively (Anxiety & Depression Association of America [ADAA], 2025; Bennett & Walkup, 2025; NIMH, 2024a).

Anxiety disorders include generalized anxiety disorder (GAD), social anxiety disorder, panic disorder (PD), separation anxiety disorder, phobias (i.e., an intense fear of places or situations that causes panic-like reactions), separation anxiety disorder, and selective mutism. Many experience anxiety episodes manifested by sweating, heart palpitations, and nervousness; all are considered normal responses when appropriately triggered and not maladaptive. Some degree of anxiety is adaptive and facilitates cautiousness in potentially dangerous situations or promotes practice, preparation, and rehearsal to improve functioning. Anxiety is considered an illness requiring treatment when triggered without a threat and when symptoms become debilitating or negatively impact an individual’s life (ADAA, 2025; Avery, 2024; Barnhill, 2023; Boland & Verduin, 2022; NIMH, 2024a).

Both environmental and genetic influences can contribute to anxiety disorders. Risk factors include childhood shyness, stress buildup, certain personality types, exposure to stressful or traumatic life events when young, comorbid psychological conditions, drug/alcohol use, and biological relatives with anxiety disorders. Additionally, anxiety may be linked to ongoing health issues (diabetes, heart disease, hyperthyroidism, respiratory disorders [asthma, chronic obstructive pulmonary disease], drug misuse, alcohol or drug withdrawal, chronic pain, irritable bowel syndrome, rare tumors that produce hormonal imbalances [pheochromocytoma]) (Barnhill, 2023; Bennett & Walkup, 2025; NIMH, 2024a).

Nonpharmacological Treatment 

CBT is an effective psychotherapy for individuals with anxiety disorders. CBT teaches individuals to rethink, respond, and react to situations to reduce anxiety and fear. CBT is the gold standard for psychotherapy when treating anxiety disorders. Exposure therapy is a form of CBT used to treat certain anxiety disorders. Exposure therapy enhances individuals’ ability to confront the fears underlying their anxiety disorder and reengages them in activities they have been avoiding, as evident in phobias. This can be done in vivo, through imagination, or via virtual reality (VR). VR therapy uses environments simulated by computer programs that feature immersion, interactivity, and imagination. Patients are provided with a virtual environment, such as the one that triggers their phobia. They identify with the specific avatars during multiple sessions until they can cope with the anxiety while preparing for exposure in real life. Additional nonpharmacological treatments include lifestyle changes (avoiding excessive caffeine, reducing or avoiding alcohol, smoking cessation, managing stress effectively [meditation, exercise, mindfulness]), which can help reduce anxiety symptoms and complement the effects of psychotherapy (Alvarez et al., 2025; Andersen et al., 2023; Bodur et al., 2024; Boland & Verduin, 2022; NIMH, 2024a; Wu et al., 2023; Zeng et al., 2025).

Pharmacological Treatment 

It is recommended that CBT be used in combination with pharmacological interventions as treatment for anxiety. SSRIs and SNRIs are the first-line agents for GAD, panic, and social anxiety disorders. These medications are well-tolerated and do not cause dependency. Commonly prescribed SSRIs are fluoxetine (Prozac) sertraline (Zoloft), citalopram (Celexa), paroxetine (Paxil), and escitalopram (Lexapro). The SNRIs venlafaxine (Effexor) and duloxetine (Cymbalta) are also effective for anxiety. Selection should be based on the adverse-effects profile, patient preference, patient history, and drug interactions (Barnhill, 2023; Gregory & Hardy, 2022; Stein & Craske, 2025). The potential adverse effects of SSRIs and SNRIs are listed in Table 3.

Other medications, such as benzodiazepines, are known to improve anxiety symptoms but are no longer recommended as first-line therapy due to their adverse-effects profile and the risk of tolerance, dependence, abuse, or misuse. For patients with severe anxiety without a history of substance misuse, a benzodiazepine may be initiated to manage symptoms until the first-line treatment reaches therapeutic levels. They are also frequently used for short-term anxiety management during minor medical procedures, such as dental work, or as presedation. Benzodiazepines enhance the effects of GABA in the brain. They promote relaxation and alleviate muscular tension and other physical symptoms of anxiety. The most commonly used benzodiazepines include clonazepam (Klonopin), alprazolam (Xanax), diazepam (Valium), and lorazepam (Ativan). Of these, diazepam (Valium) and clonazepam (Klonopin) are the most widely used for anxiety due to their rapid onset and long half-life, which can decrease the risk of withdrawal symptoms when discontinued. Adverse effects of benzodiazepines include drowsiness or tiredness, dizziness, nausea, blurred vision, headache, confusion, and nightmares (Garakani et al., 2021; O’Leary & Khan, 2024; Stein & Craske, 2025).

Buspirone (Buspar) can be used as an adjunct treatment for individuals who do not experience a complete response to treatment with an SNRI or SSRI and CBT. Buspirone (Buspar) acts as a partial agonist of serotonin receptors. Buspirone (Buspar) must be taken daily as it is ineffective when used as needed. Treatment should be continued for at least 4–6 weeks before determining its effectiveness. Adverse effects of buspirone (Buspar) include dizziness, headache, nausea, nervousness, lightheadedness, excitement, and insomnia (Garakani et al., 2021; O’Leary & Khan, 2024; Stein & Craske, 2025).

Propranolol (Inderal) is a noncardioselective beta blocker that can help alleviate the physical symptoms of anxiety due to stage fright/performance anxiety (sweating, trembling, hyperventilation, tachycardia). Typical dosing is 40 mg administered 1 hour before participating in the anxiety-causing activity. Adverse effects include hypotension, bradycardia, dizziness, weakness, fatigue, and cold hands (Szeleszczuk & Fraczkowski, 2022). For more information on anxiety disorders, refer to the NursingCE course on Anxiety.

             

Bipolar Disorder

Bipolar disorder, formerly known as manic depression, is characterized by unusual shifts in an individual’s mood, activity level, and concentration. Bipolar disorder affects approximately 2.8% of adults in the United States (Depression and Bipolar Support Alliance [DBSA], n.d.; NAMI, n.d.; NIMH, 2024c). There are currently four classifications:

• Bipolar I disorder: characterized by the presence of at least one lifetime manic episode lasting at least 1 week (or any duration if hospitalization is required); a manic episode is a period of abnormally elevated or irritable mood, overactivity, racing thoughts, rapid speech, inflated self-esteem, and decreased need for sleep, usually interspersed with depressed periods; may also experience hypomania (like mania but less severe) or an MDE, but this is not required for diagnosis
• Bipolar II disorder: characterized by the presence of at least one lifetime MDE and hypomanic episode lasting at least 4 days without a history of mania; is no longer considered less severe than bipolar I disorder due to mood instability and effect on the individual’s social and work life
• Cyclothymic disorder: characterized by at least 2 years (1 year for children) of hypomanic or depressive symptoms without meeting the criteria for an episode of hypomania, mania, or major depression
• Other specified and unspecified bipolar: bipolar disorder-like symptoms that do not match any of the above three categories, such as symptoms induced by substance misuse or caused by certain medical conditions (Cushing’s disease, multiple sclerosis [MS], or stroke) (APA, 2022)

While the exact cause of bipolar disorder is still unknown, it is hypothesized to be some combination of altered brain structure or function, genetics, and environmental factors. Neuroimaging in patients with bipolar disorder has shown fewer connections in the limbic structures and prefrontal networks, mostly in the amygdala. Immune dysfunction is hypothesized due to elevated inflammatory markers in persons with bipolar disorder. Family studies have demonstrated that genetic factors are influential in bipolar disorder pathogenesis, but specific genes have not been identified. Patients with bipolar disorder are at higher risk for thyroid disease, migraines, heart disease, diabetes, obesity, and other physical illnesses. Individuals diagnosed with bipolar disorder are also more likely to suffer from other mental health disorders (anxiety, ADHD, or SUD). Symptoms of a depressive episode match the symptoms of depression described above. The behavior present in a manic episode may include the previously mentioned symptoms as well as disorganized or nonlinear patterns of thoughts or speech and risk-taking behaviors (excessive spending, gambling, or sexual promiscuity). Hypomanic episodes may present as the individual feeling excellent, being highly productive, and functioning well. Due to this, many individuals with bipolar II disorder are diagnosed during an MDE, as some may view the symptoms of hypomania as desirable. Hypomania may develop into full mania if left untreated. Some patients with bipolar I disorder may also suffer from psychotic features, such as delusions or hallucinations when experiencing a manic episode (APA, 2022; NIMH, 2024c; Stovall, 2025).

Psychosocial risk factors include a first-degree relative with bipolar disorder, older paternal age, a stressful or traumatic childhood life event, and drug or alcohol use. It is typically diagnosed in the teenage years or early 20s. If left untreated, bipolar disorder can lead to drug or alcohol misuse, legal or financial problems, damaged relationships, and poor work or school performance. It is considered the sixth leading cause of disability worldwide, resulting in an average decrease in life expectancy by 9.2 years. Suicide risk is 5 times higher in patients diagnosed with bipolar disorder than in the general population, and approximately 10%–20% of individuals diagnosed with bipolar disorder die by suicide (APA, 2022; DBSA, n.d.; Ostacher, 2025; Stovall, 2025).

Treatment

Bipolar disorder is a lifelong illness requiring consistent and regular treatment, as symptoms will return over time. Treatment includes psychotherapy, circadian rhythm interventions, and medication management to control symptoms. Psychotherapy may consist of CBT, family-focused therapy, or psychoeducation and, in severe cases, may require ECT or repetitive transcranial magnetic stimulation (rTMS). Circadian rhythm-based therapies include bright light therapy, interpersonal and social rhythm therapy (IPSRT), and total sleep deprivation (NIMH, 2024c; Oliva et al., 2024).

The complex goals of therapy include treatment of acute hypomania or mania, depression, prevention of mood relapses, and symptom management during subacute episodes. Medications for bipolar disorder may include mood stabilizers, atypical antipsychotics, and antidepressants (Oliva et al., 2024). Lithium (Lithobid) is a commonly prescribed mood stabilizer that alters sodium transport across neurons (NIMH, 2023b). According to the International Society for Bipolar Disorders (ISBD), lithium (Lithobid) alone is recommended as the first-line treatment for acute mania and maintenance therapy of bipolar I disorder. It is considered the first-line treatment for acute depression in bipolar I disorder. It is also considered first-line maintenance treatment and second-line treatment for acute depression in bipolar II disorder. There is moderate concern about long-term safety and tolerability with lithium (Lithobid) use, as it is considered hazardous in pregnant and breastfeeding individuals. Common adverse effects include tremor, polyuria/polydipsia (excessive urination/thirst), weight gain, GI disturbances (diarrhea, vomiting), drowsiness, and cognitive impairment. More serious potential reactions include seizures, ventricular arrhythmias, syncope, and coma (Janicak, 2024; Keramatian et al., 2023; Yatham et al., 2018).

Alternatives for mood stabilization include antiseizure drugs (ASDs; divalproex sodium [Depakote], carbamazepine [Tegretol], lamotrigine [Lamictal]). Divalproex sodium (Depakote) is first-line monotherapy for acute mania and maintenance therapy of bipolar I disorder, second-line for acute depressive episodes in bipolar I disorder, third-line for maintenance treatment in bipolar II disorder, and third-line for acute depression treatment in bipolar II disorder. Carbamazepine (Tegretol) is considered a second-line treatment in acute mania. It can be used for maintenance treatment, but it is considered a second-line treatment for bipolar I disorder and a third-line treatment for bipolar II disorder. Lamotrigine (Lamictal) is not recommended for acute mania. It is considered a first-line treatment for maintenance therapy of bipolar I disorder, first-line treatment for acute depression in bipolar I disorder, second-line for acute depression in bipolar II disorder, and first-line maintenance treatment for bipolar II disorder (Keramatian et al., 2023; Yatham et al., 2018).

Regarding safety and tolerability for long-term use, divalproex sodium (Depakote) has moderate safety and minor tolerability concerns, carbamazepine (Tegretol) has minor safety and moderate tolerability concerns, and lamotrigine (Lamictal) has minimal safety or tolerability concerns. The disadvantages of most mood stabilizers include their renal toxicity and the need for initial serum drug levels to be monitored until dosing is stable and then periodically to rule out toxicity (this is true for lithium [Lithobid], divalproex sodium [Depakote], and carbamazepine [Tegretol]). Mood stabilizers are also associated with several adverse effects, including itching, rash, polydipsia, polyuria, tremors, nausea, vomiting, slurred speech, tachycardia, bradycardia, irregular heartbeat, loss of consciousness, changes in vision, seizures, hallucinations, loss of coordination, and angioedema (NIMH, 2023b; Woods, 2023).

              Second-generation antipsychotics (SGAs, or atypical)) help treat the symptoms of agitation, delusions, and hallucinations often seen in bipolar disorder. This may include quetiapine (Seroquel), asenapine (Saphris), aripiprazole (Abilify), paliperidone (Invega), risperidone (Risperdal), olanzapine (Zyprexa), ziprasidone (Geodon), cariprazine (Vraylar), clozapine (Clozaril), lumateperone (Caplyta), and lurasidone (Latuda). These drugs function mainly by antagonizing dopamine D2 and serotonin 5-HT2A receptors in the brain, except for aripiprazole (Abilify) and cariprazine (Vraylar), which function as partial dopamine and serotonin 5-HT1A agonists and 5-HT2A antagonists. As a class, adverse effects for this group of drugs may include drowsiness, dizziness, restlessness, weight gain, anticholinergic effects, nausea, vomiting, hypotension, seizures, and leukocytopenia (NIMH, 2023b; Woods, 2023). Antipsychotics will be discussed in greater depth in the section on schizophrenia.

According to the ISBD, there is evidence to support the use of quetiapine (Seroquel), asenapine (Saphris), aripiprazole (Abilify), paliperidone (Invega), risperidone (Risperdal), and cariprazine (Vraylar) for the treatment of acute mania. It is estimated that as many as 50% of patients will experience significant improvement with monotherapy within 3–4 weeks. Combination therapy increases this by about 20% and may benefit patients with a history of partial response to monotherapy, with psychotic mania, or where rapid response is desired. In those cases, evidence supports combining lithium (Lithobid) or divalproex sodium (Depakote) with quetiapine (Seroquel) or risperidone (Risperdal). There is also evidence supporting the use of olanzapine (Zyprexa) either as monotherapy or with lithium (Lithobid), divalproex sodium (Depakote), carbamazepine (Tegretol), or ziprasidone (Geodon) as second-line treatment for acute mania (Keramatian et al., 2023; NIMH, 2023b; Yatham et al., 2018).

The FDA has approved five antipsychotic medications for the treatment of acute bipolar depression, including olanzapine/fluoxetine (Symbyax), quetiapine (Seroquel), lurasidone (Latuda), cariprazine (Vraylar), and lumateperone (Caplyta). Lithium (Lithobid) and lamotrigine (Lamictal) are often used concurrently as therapy for bipolar depression, despite less robust evidence for lithium’s (Lithobid’s) effect on depression. SSRIs, SNRIs, and bupropion (Wellbutrin) are sometimes used as an adjunct for acute depressive symptom management in bipolar disorder. According to the ISBD, these drugs should not be used as monotherapy in patients with bipolar I disorder and acute depression. However, there is evidence supporting their use as second-line adjunctive therapy (with lithium [Lithobid], divalproex sodium [Depakote], or an SGA) for acute depression. In patients with bipolar II disorder, there is evidence suggesting that bupropion (Wellbutrin), sertraline (Zoloft), or venlafaxine (Effexor) are appropriate second-line treatments when used as adjuncts for acute depression, and a third-line option includes fluoxetine (Prozac). For long-term maintenance therapy in patients with bipolar II disorder, there is evidence supporting the use of venlafaxine (Effexor) as a second-line treatment and escitalopram (Lexapro), fluoxetine (Prozac), or other antidepressants as third-line treatment options only (Bobo & Shelton, 2025; Coryell, 2026a; Keramatian et al., 2023; Oliva et al., 2024; Yatham et al., 2018).

For long-term maintenance therapy of bipolar disorder, psychotherapy in combination with pharmacological treatment is advised. It is recommended to continue using the medication that was effective for acute treatment. There is evidence supporting the use of quetiapine (Seroquel), asenapine (Saphris), or aripiprazole (Abilify) either as monotherapy or combined with lithium (Lithobid) or divalproex sodium (Depakote) as first-line treatment of bipolar I disorder. Evidence also supports using olanzapine (Zyprexa) or risperidone (Risperdal) as second-line maintenance treatment options in bipolar I disorder. In bipolar II disorder, evidence supports using quetiapine (Seroquel) as a first-line treatment for acute depression or long-term maintenance therapy. Second-line treatment options for long-term maintenance treatment of bipolar II disorder include venlafaxine (Effexor), and third-line treatment options include carbamazepine (Tegretol) or risperidone (Risperdal), primarily to prevent hypomania episodes. Regarding safety and tolerability, there are more concerns with olanzapine (Zyprexa), quetiapine (Seroquel), and risperidone (Risperdal) than with the other SGAs discussed here, especially when combined with lithium (Lithobid) or divalproex sodium (Depakote; Keramatian et al., 2023; Yatham et al., 2018).

Schizophrenia

According to the WHO, approximately 23 million people (1 in 345 people) are affected by schizophrenia worldwide. The lifetime risk of schizophrenia is approximately 0.3%–0.7%. This severe mental disorder typically begins in late adolescence or early adulthood and is characterized by psychoses or distortions in thinking, perception, emotions, language, behavior, or sense of self. Individuals diagnosed with schizophrenia have a life expectancy of 10–25 years lower than the general population (APA, 2022; WHO, 2025b; Zhan et al., 2025).

The pathogenesis of schizophrenia is complex, consisting of environmental and genetic interactions. Multiple studies suggest that schizophrenia results from abnormalities in several neurotransmitters—including dopaminergic, serotonergic, and alpha-adrenergic hyperactivity or glutaminergic and GABA hypoactivity—due primarily to genetics. For this reason, obtaining a complete history is essential. An individual with a caregiver diagnosed with schizophrenia has a 40% risk of developing the disease, and environmental factors further increase the risk. Questions should be asked regarding birth weight, the presence of gestational diabetes, birth via an emergency cesarean section, maternal nutritional deficiencies, birth month, and the type and location of their childhood residence. Ethiopian, Moroccan, or Caribbean migrants and their children have a significantly greater risk, up to fourfold, of developing schizophrenia than those of other descent. It is hypothesized that social discrimination and a deficiency in vitamin D are impactful in the development of schizophrenia in immigrants moving north. Cannabis use and smoking are associated with schizophrenia and should be addressed when obtaining a health history (Fischer & Buchanan, 2026; Hany & Rizvi, 2024).

Symptoms of schizophrenia are categorized as positive (hallucinations, delusions, disorganized thoughts and speech, repetitive movements), negative (diminished emotional expression, avolition, alogia, anhedonia, asociality), or cognitive (poor executive functioning, decreased focus/attention, poor working memory). Negative symptoms contribute to the morbidity of schizophrenia and are not as commonly experienced with other psychotic disorders (APA, 2022). Risk factors for schizophrenia include:

• age:

• males: peak onset of symptoms between early to mid-20s
• females: peak onset of symptoms between the late 20s to early 30s
• the onset of symptoms seldom occurs past 45 years of age and rarely before puberty
• sex differences may be linked to the effects of estrogen on females

• sex: males exhibit more negative symptoms and experience more cognitive impairment than females; females experience more mood symptoms
• family history increases risk by 10%
• intrauterine infections, a traumatic delivery, or trauma during pregnancy increase the risk of the fetus developing schizophrenia
• season of birth: individuals born in late winter or early spring (defined as February or March in the northern hemisphere) have a higher incidence of schizophrenia
• growing up in an urban environment is associated with a higher incidence of schizophrenia
• environmental stressors

• relationship stress
• difficulties at school or work
• heavy cannabis use
• people with schizophrenia misuse alcohol and drugs more frequently than the general population (APA, 2022; Boland & Verduin, 2022; Fischer & Buchanan, 2026)

Treatment

Treatment for schizophrenia is multifactorial and lifelong and includes pharmacological management and psychosocial support. A psychiatrist usually guides treatment, and due to the complexity of the diagnosis, treatment in a coordinated specialty care (CSC) program is recommended. CSC is a recovery-oriented team approach that involves case managers, family members, social workers, and educational and employment services. Research has demonstrated that CSC is more effective than typical treatment alone. Patients participating in CSC experience more effective treatment management, improved quality of life, and more involvement in social settings such as work or school. Due to these documented benefits, CSC has become the standard of care per the APA practice guideline for patients diagnosed with schizophrenia. ECT is a treatment recognized as beneficial to patients with psychosis related to schizophrenia that is unresponsive to pharmacotherapy. According to the APA, using ECT as an adjunct therapy to treatment with antipsychotics increases the remission rate. ECT is also beneficial when initiated for patients who require emergent treatment or those with an increased risk of suicide (APA, 2020; Keshavan, 2025b; NIMH, 2022).

Pharmacotherapy includes managing the acute phase, followed by maintenance therapy aimed at improving socialization, self-care, and mood. The rationale for maintenance treatment is to prevent relapse. Medication management aims to control symptoms with the lowest effective dose and the fewest adverse effects. In many cases, combination therapy with multiple medications is necessary to gain adequate control over the condition. Identifying the proper medication combination and dosing levels can take time to achieve the desired outcome. While it can take several weeks to notice an improvement in symptoms, prompt initiation of medication therapy is recommended. It should occur as close to the first acute episode as possible, as a significant amount of illness-related brain changes occur within the first 5 years after onset (Freudenreich & McEvoy, 2025; Keshavan, 2025a, 2025b; Marder, 2026; Shen et al., 2023; Stroup & Marder, 2026).

According to the APA (2020) practice guidelines for treating patients with schizophrenia, SGAs are considered first-line and maintenance treatment. While the selection of the type of antipsychotic agent depends on various individual patient factors, SGAs are generally preferred over first-generation antipsychotics (FGAs) due to their superior adverse-effects profile. The APA guideline also acknowledges that an evidence-based algorithm approach to antipsychotic selection is unavailable due to limitations in clinical trial designs and a lack of direct drug-to-drug comparisons. There are no benefits of using one antipsychotic over another, except for clozapine (Clozaril). Clozapine (Clozaril) is the only medication within the class of SGAs that is not recommended as first-line treatment, as it carries a risk for life-threatening agranulocytosis. Clozapine (Clozaril) is reserved for patients whose symptoms are resistant to treatment with other antipsychotic drugs. It is the most effective antipsychotic drug for managing treatment-resistant schizophrenia (APA, 2020; Freudenreich & McEvoy, 2025; Stroup & Marder, 2026).

The 2020 APA treatment guideline recommends that drug selection is premised on the risks and benefits of the prescribed therapy, individual patient factors such as coexisting medical conditions, the potential for those conditions to be affected by medication adverse effects, the risk for drug interactions, psychosocial support, patient and family preference, as well as the feasibility of compliance with the chosen therapy. In addition, all psychotropic medications appear to cross the placenta and have been found in amniotic fluid and human breast milk. Untreated or inadequately treated maternal psychiatric illness can result in poor adherence to prenatal care, inadequate nutrition, increased alcohol or tobacco use, and disruptions to the family environment and parent-infant bonding (APA, 2020; Stroup & Marder, 2026).

FGAs and SGAs are available in IR and ER oral formulations, short-acting IM, and long-acting injectable (LAI) agents. LAI medications are a practical option for patients who are nonadherent with oral medication therapy. However, HCPs are advised to determine the cause of the patient’s nonadherence to oral treatment before switching to LAI. If nonadherence is due to adverse effects of oral treatment, the patient should be switched to an alternative oral medication before transitioning to LAI. Agitation and hallucinations typically resolve first (within days), but delusions may take weeks to resolve, and full effects are usually seen within 6 weeks; some antipsychotic medications require strict monitoring as outlined by the FDA REMS drug program, which is reserved for drugs with serious safety concerns to help ensure the benefits of the medication outweigh the risks. REMS is designed to mitigate the occurrence and severity of certain risks by enhancing the safe use of high-risk medications, as described in the FDA-approved prescribing information, through heightened monitoring and surveillance of patients receiving these medications (APA, 2020; FDA, 2025a; NIMH, 2023a; Stroup & Marder, 2026).

First-Generation Antipsychotics

FGAs work by antagonizing dopamine D2 receptors. They are classified as either high- or low-potency. High-potency FGAs carry a higher risk of extrapyramidal symptoms (EPS) and a lower risk of anticholinergic effects, sedation, or weight gain. The low-potency FGAs carry a lower risk of EPS but a higher risk of sedation and anticholinergic effects. Some of the most common high-potency FGAs are haloperidol (Haldol), fluphenazine (Prolixin), loxapine (Loxitane), perphenazine (Trilafon), thiothixene (Navane), pimozide (Orap), and trifluoperazine (Stelazine). Common low-potency FGAs include chlorpromazine (Thorazine) and thioridazine (Mellaril). FGAs pose the highest risk for EPS among all antipsychotic medications. EPS are drug-induced movement disorders among the most common adverse effects of centrally acting dopamine-receptor-blocking medications. EPS are often debilitating and interfere with communication, socialization, motor skills, and activities of daily living. These symptoms can include acute dystonia (spasms of the tongue, neck, face, and back), parkinsonism (tremor, shuffling gait, drooling, instability, stooped posture), akathisia (compulsive, repetitive movements, agitation), and tardive dyskinesia (lip-smacking, worm-like tongue movements). Other less common adverse effects of FGAs include orthostasis, QT prolongation, weight gain, seizures, hyperlipidemia, and glucose abnormalities (APA, 2020; D’Souza et al., 2025; Jibson, 2025a). Refer to Table 3 for a detailed overview of the special considerations of several FGAs.

Table 3

Common Types of FGAs

Medication	Special Considerations
Chlorpromazine (Thorazine)	IM injection should be administered to the upper outer quadrant of the gluteal area
Haloperidol (Haldol)	Hypersensitivity can include anaphylaxis and angioedema
Fluphenazine (Prolixin)
Loxapine (Loxitane) Loxapine (Adasuve) inhaler	Loxapine (Adasuve) inhaler is used to treat agitation and requires participation in the REMS program due to the risk of bronchospasm
Thioridazine (Mellaril)	Risk for dose-related QTc prolongation
Thiothixene (Navane)	Smoking may interfere with cytochrome P450 1A2 (CYP1A2) induction, impairing drug metabolism
Trifluoperazine (Stelazine)	Smoking may interfere with CYP1A2, impairing drug metabolism

(APA, 2020; Woods, 2023)

Second-Generation Antipsychotics

Examples of SGAs include quetiapine (Seroquel), asenapine (Saphris), aripiprazole (Abilify), brexpiprazole (Rexulti), paliperidone (Invega), risperidone (Risperdal), olanzapine (Zyprexa), ziprasidone (Geodon), cariprazine (Vraylar), lurasidone (Latuda), and clozapine (Clozaril). SGAs antagonize dopamine D2 and serotonin 5-HT2A receptors in the brain, except for aripiprazole (Abilify) and cariprazine (Vraylar), which function as partial dopamine and serotonin 5-HT1A agonists and 5-HT2A antagonists. Clozapine (Clozaril) also works differently by antagonizing alpha-adrenergic and muscarinic cholinergic receptors. EPS will occur less frequently with SGAs than with FGAs; however, EPS risk increases with dose escalation. As a class, SGAs pose a risk for metabolic adverse effects (weight gain, hyperlipidemia, seizures, diabetes), contributing to the increased risk of cardiovascular mortality in patients diagnosed with schizophrenia. Less commonly, SGAs can cause orthostasis and QTc prolongation (APA, 2020; D’Souza et al., 2025; Jibson, 2025b). Refer to Table 4 for a detailed overview of the special considerations of common SGAs.

Table 4

Common Types of SGAs

Medication	Special Considerations
Quetiapine (Seroquel)	IR forms are only marginally affected by food, whereas ER forms are significantly affected if consumed with a high-fat meal Taking ER tablets on an empty stomach or with a snack of fewer than 300 calories is recommended
Lurasidone (Latuda)	It must be administered with a snack or meal of at least 350 calories
Olanzapine (Zyprexa)	IM administration is primarily used when the patient presents with severe agitation
Risperidone (Risperdal)
Cariprazine (Vraylar)
Clozapine (Clozaril)	Reserved for treatment-resistant schizophrenia Only available through a REMS program due to the risk for life-threatening agranulocytosis, which is a decline in the white blood cell count, namely the absolute neutrophil count (ANC) Increases the risk for orthostatic hypotension and seizures
Ziprasidone (Geodon)	This is used for the acute treatment of agitation in schizophrenia There is an increased risk of bone fractures with long-term use.

(APA, 2020; Jibson, 2025b; Woods, 2023)

Monitoring of Patients on Antipsychotics

While several important monitoring domains are required for patients on antipsychotic medications, adherence is one of the most common problems that impair effective outcomes. Monitoring for adverse effects is essential, as they are most commonly associated with treatment nonadherence and discontinuation. Some adverse effects of treatment will improve over time, whereas others may worsen with dose escalation. Early in treatment, the most common adverse effects include sedation, fatigue, orthostatic hypotension, and anticholinergic effects (dry mouth, constipation, difficulty urinating). As treatment progresses, many of these adverse effects dissipate or improve. In contrast, adverse effects corresponding with metabolic syndrome (weight gain, hyperlipidemia, hyperglycemia) worsen as the duration of therapy increases. Furthermore, EPS can also worsen with dose escalation of antipsychotics, particularly FGAs. All types of antipsychotics are associated with sexual dysfunction, including loss of libido, anorgasmia, erectile dysfunction, and ejaculatory disturbances such as retrograde ejaculation (APA, 2020; Stroup & Marder, 2026).

For more information on schizophrenia, refer to the NursingCE course on Psychotic Disorders.

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