Psychotic Disorders Nursing CE Course for RNs and LPNs

phrenia (the most common of the psychotic disorders), schizophreniform disorder, peripartum psychosis, psychotic disorder due to another medical condition, and substance-induced psychotic disorder (APA, 2022). Table 2 summarizes the characteristics of each of these conditions.

 

Table 2

Specific Characteristics of Each Psychotic Disorder

Disorder	Characteristics
Brief psychotic disorder	Characterized by a sudden and short period of psychotic behavior, typically in response to a traumatic event such as the death of a loved one; symptoms last longer than 1 day but resolve within 1 month of symptom onset
Delusional disorder	Characterized by the presence of delusions for at least 1 month in the absence of any other key features of psychotic disorders
Schizoaffective disorder	Characterized by the presence of active-phase symptoms (e.g., hallucinations, delusions, negative symptoms, and disorganized speech) at the same time as a mood episode; active-phase symptoms are present either 2 weeks before or 2 weeks after the appearance of the mood episode
Schizophrenia	Characterized by the presence of at least two active-phase symptoms for 1 month with behavior changes lasting at least 6 months
Schizophreniform disorder	Includes symptoms of schizophrenia lasting at least 1 month but no more than 6 months without a functional decline
Psychosis with peripartum onset	Symptoms may appear in as little as 24 hours after delivery and include hallucinations and/or delusions that can lead to suicide or injury to others, including the infant
Psychotic disorder due to another medical condition	Symptoms of psychosis develop due to an unrelated medical condition
Substance-induced psychotic disorder	Symptoms may be caused by drug withdrawal from hallucinogens such as crack cocaine, amphetamine, methamphetamine, alcohol, or cannabis; symptoms may also result from exposure to a toxin or as an adverse effect of some medications

(APA, 2022)

 

Impact of Psychotic Disorders

Approximately 1.5–3.5% of the population has a psychotic disorder. Although each psychotic disorder has a variable age of onset, psychotic disorders generally appear in the late adolescent years to the early 30s, and individuals of both sexes are impacted equally. Psychotic disorders can severely affect the patient, family members, and friends (Calabrese & Khalili, 2023).

Each psychotic disorder has a different prevalence. Approximately 2–7% of initial-onset psychotic episodes are diagnosed as a brief psychotic disorder. The lifetime prevalence of delusional disorder is approximately 0.02–0.2%. The most common delusional subtype is persecutory. Generally, there is no difference in the prevalence between males and females, except for the jealous subtype, which is more common in males. The estimated lifetime prevalence of psychotic disorders due to another medical condition is 0.21–0.54%. When prevalence is separated by age, those over 65 have the highest prevalence at 0.74%. However, due to the number of disorders that can cause psychosis, it is difficult to determine the prevalence accurately. The prevalence of substance-induced psychotic disorder is not known; however, substance-induced psychotic disorder accounts for 7–25% of initial psychotic episodes. The most common psychotic disorder is schizophrenia. According to the World Health Organization (WHO), approximately 24 million people (0.32%) 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 10–20 years lower than the general population. Schizoaffective disorder is approximately 33% less common than schizophrenia. This is likely due to the mood component included in the diagnostic criteria (APA, 2022; WHO, 2025).

As many as 100 million people globally lack housing, and over 1.6 billion lack adequate housing. Two million individuals who lack housing live in high-income countries. The lifetime prevalence of being without housing in the United States is 4.2%. Each day, 550,000 Americans do not have a regular residence. Approximately 25–50% of those without housing are found to have a psychiatric disorder. Recent data indicate as high as a 77% lifetime prevalence of any mental health disorder among those without housing. Adults without housing have a high incidence of schizophrenia and other psychotic disorders due to the associated challenges of maintaining employment or making appropriate decisions regarding their living conditions and self-care. Schizophrenia and other psychotic disorders are also associated with a high level of disability, substance use, alcohol use, and suicide (Barry et al., 2024; Gutwinski et al., 2021).

Pathophysiology

An imbalance in neurotransmitters in the brain can cause psychotic disorders. There is a strong link between psychotic disorders and dopamine. The positive symptoms (e.g., hallucinations, delusions, and repetitive movements) experienced with some psychotic disorders are believed to result from increased dopamine within the mesolimbic tract. Studies have also shown that decreased N-methyl-d-aspartate (NMDA) glutamate receptor function is associated with psychotic disorders, which can account for the presence of hallucinations, delusions, agitation, and mood alterations. Some studies have also linked psychotic disorders to an imbalance of acetylcholine based on the smoking habits of those with psychotic disorders. Nicotine can increase acetylcholine function, and researchers have observed a slight improvement in symptoms following nicotine consumption (Calabrese & Khalili, 2023). 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.

Risk Factors

Many risk factors can increase the likelihood of an individual being diagnosed with a psychotic disorder. There is strong evidence that psychotic disorders have a genetic component. Therefore, individuals who have a family member with a psychotic disorder are more likely to be diagnosed. A brain injury during fetal development or childhood also increases the risk of developing a psychotic disorder (Calabrese & Khalili, 2023). Table 3 identifies risk factors for each type of psychotic disorder.

Table 3

Risk Factors for Each Psychotic Disorder

Disorder	Risk Factors
Brief psychotic disorder	Age: average age at onset is the mid-30s; however, onset can occur across the lifespan Biological sex: more common in females than males Major life events causing severe emotional distress may be an isolated stressful event or series of events the stressor may be unrelated to the psychotic episode Lower socioeconomic status Personal history of a personality disorder Family history of mood disorders (bipolar) or psychotic disorders
Delusional disorder	Age: middle to late adulthood Biological sex: jealous type is slightly more common in males than females Personal history of living in a hostile environment with an overly controlling parent who is distant or exhibits sadistic behaviors Social isolation Achievements less than expected or desired by the individual
Schizoaffective disorder	Age: typical age at onset is early adulthood; however, onset can occur across the lifespan Biological sex: more common in females Family history of a first-degree relative diagnosed with schizoaffective disorder, bipolar disorder, or schizophrenia Diagnosis with another psychotic disorder; the emergence of mood disturbances is sometimes not initially recognized
Schizophrenia	Age: males: peak onset of symptoms 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 and rarely before puberty biological sex differences may be linked to the effects of estrogen on females Biological sex: males exhibit more negative symptoms and experience more cognitive impairment than females; females experience more mood symptoms 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 abuse alcohol and drugs more frequently than the general population An individual with one parent diagnosed with schizophrenia has a 10% risk of developing the disease. Environmental factors further increase the risk. Children of Americans of African American or Caribbean descent have a 10 times greater risk of developing schizophrenia than Americans of European descent.
Schizophreniform disorder	Age: adolescents and young adults the peak onset in females is late 20s the peak onset in men is late adolescence to early 20s Biological sex: equally distributed between males and females Relatives of those with schizophreniform disorder are more likely to have a psychotic mood disorder than relatives of those with bipolar disorders without psychosis
Peripartum psychosis	Age: pregnant patients over 35 years are 2.4 times more likely to develop psychosis with peripartum onset Low infant birth weight Preterm birth Personal or family history of bipolar disorder Previous psychotic episode
Psychotic disorder due to another medical condition	Development of a condition that can cause a psychotic episode such as multiple sclerosis, systemic lupus erythematosus (SLE), undiagnosed or poorly managed endocrine or metabolic disorders (e.g., hypoglycemia), temporal lobe epilepsy, Huntington’s disease, Parkinson’s disease, sensory deprivation, migraines, vitamin B12 deficiency, electrolyte imbalance, hepatic failure, renal failure, infectious diseases
Substance-induced psychotic disorder	Intoxication because of medication or illicit substance abuse, such as alcohol, sedatives, hypnotics, and anxiolytics Withdrawal from alcohol, cannabis, hallucinogens, inhalants, sedatives, hypnotics, anxiolytics, and stimulants Use of anesthetics, analgesics, anticholinergics, antiseizure medications, antihistamines, antihypertensive and other cardiovascular medications, antimicrobials, antiparkinsonians, corticosteroids, chemotherapeutic agents, gastrointestinal medications, muscle relaxants, nonsteroidal anti-inflammatories (NSAIDs), antidepressants, and over-the-counter (OTC) medications such as phenylephrine (Sudafed PE, Dimetapp) or pseudoephedrine (Sudafed, Allegra-D, Zyrtec-D)

                                                                                                (APA, 2022; Boland & Verdiun, 2022)

Diagnosis

While each psychotic disorder has unique diagnostic criteria, there are similarities in manifestations. Clinical manifestations commonly seen across each diagnosis include delusions, paranoia, visual or auditory hallucinations, a general decline in the individual’s ability to make decisions and care for themselves, cognitive dysfunction, and negative symptoms. Healthcare providers (HCPs) must obtain a complete history that includes the severity of symptoms, duration, medical history, and history of trauma, abuse, or substance use. At times, the patient may not be the best historian, and HCPs must be able to recognize the signs of an underlying psychotic disorder (Calabrese & Khalili, 2023).

Brief Psychotic Disorder

The defining manifestations of brief psychotic disorder are the presence of at least one key feature of psychosis and the duration of symptoms. The patient must present with symptoms that last a full day but not more than 30 days and then resolve completely (APA, 2022, pp. 108, 109).

The patient’s symptoms are not directly related to the use of a substance, medication, or preexisting medical diagnosis or health concern. They are also not due to a more appropriate psychiatric condition such as major depressive disorder (MDD) or bipolar disorder with psychotic features. Episodes may immediately follow a traumatic life event (with a marked stressor) or following the birth of a child (peripartum onset; APA, 2022, pp. 108, 109).

If a major mood component exists in addition to the brief psychotic disorder previously described, then schizoaffective disorder is diagnosed. However, even with treatment, patients who have an affective disorder with psychosis do not typically return to their pre-illness baseline within 30 days as with brief psychotic disorder. Schizophrenia spectrum disorders are typically differentiated by symptoms lasting longer than 30 days. Those with a personality disorder such as borderline personality disorder may have episodic incidents of psychosis primarily induced by stress lasting a day or less with complete resolution. Illnesses such as metastatic cancer, head trauma, syphilis, or thyrotoxicosis may mimic symptoms of brief psychotic disorder. Still, a thorough history and physical, along with laboratory testing and imaging, can help reveal the causal condition (Stephen & Lui, 2023).

Delusional Disorder

A diagnosis of delusional disorder is based on patient presentation and the duration of symptoms. To meet the criteria, the patient must present with at least one delusion (i.e., a misconception, belief, or thought that is firmly held despite not being grounded in reality) lasting at least 1 month. The patient should not meet the initial criteria for schizophrenia. The patient’s behavior and ability to function should be relatively unchanged from baseline without apparent dysfunction or peculiar behaviors. If the patient reports hallucinations, they must be secondary to the delusions and associated with the primary delusion (e.g., hearing the voices of aliens related to a delusion of being controlled by aliens). If mood symptoms are present, they are short in duration compared to the delusion. The patient’s delusion is not directly related to the use of a substance, medication, or preexisting medical diagnosis or health concern, and it cannot be attributed to a more appropriate psychiatric condition (APA, 2022, pp. 104, 105).

An individual experiencing delusional disorder is usually stable otherwise (i.e., exhibits behavior that would be considered normal for an individual without delusions). They are typically hypersensitive, with ego defense mechanisms like projection (putting undesirable feelings or emotions onto someone else rather than dealing with them), denial (refusing to admit that something is real), or reaction formation (denying unacceptable or threatening unconscious impulses and replacing them in consciousness with their opposite). When social isolation, distrust, low self-esteem, suspicion, or envy becomes unbearable, the individual may seek an explanation and form a delusion as the solution to these factors. Special populations at risk for delusions are immigrants with language barriers, the deaf and visually impaired, and older adults (APA, 2022, pp. 104, 105; Joseph & Siddiqui, 2023).

Schizoaffective Disorder

To make a diagnosis of schizoaffective disorder, the patient must present with manifestations of a major depressive episode (MDE) or mania, including poor or sad mood for the majority of the day on most days. Additionally, they must report at least two primary symptoms of schizophrenia. Schizoaffective disorder is a frequently misdiagnosed psychiatric disorder in clinical practice. Some researchers have considered removing the diagnosis from the Diagnostic and Statistical Manual of Mental Disorders (DSM) altogether. Since the disorder is part of a spectrum sharing criteria with other psychiatric disorders, it can be challenging to diagnose correctly. Originally, it was a subtype of schizophrenia but was eventually recognized as a separate condition. However, there were no significant studies of etiology or pathophysiology as evidence. As many as 50% of those with schizophrenia may also have comorbid depression. Mood disorders and schizophrenia have correlated risk factors, including genetics, social factors, stress, or trauma, thus increasing the risk of two different diagnoses or a single diagnosis of schizoaffective disorder (Wy & Saadabadi, 2023).

Schizophrenia

The characteristics associated with schizophrenia are multifocal, involving changes in the patient’s cognitive, behavioral, and emotional states; however, no particular symptom is indicative of a schizophrenia diagnosis. The diagnosis is based on clinical presentation, patient history, symptom presentation, and duration (APA, 2022, pp. 113, 114). To confirm the diagnosis, at least two of the following symptoms must be present for a substantial period over a month or more:

• speaking incoherently without logical organization*
• a misconception, belief, or thought that is firmly held despite not being grounded in reality*
• illusions or perceived experiences that do not exist (e.g., sounds, voices, smells, visions, feelings, etc.) *
• actions that are chaotic or confused, repetitive or purposeless, or significantly reduced (or absent) movement and speech (with catatonia)
• decreased display of emotion or a lack of motivation

• *at least one of the two symptoms displayed must be among the first three symptoms described previously (APA, 2022, pp. 113, 114)

An incidence of this disorder should persist for more than 6 months, with symptoms present for at least 1 month of that period unless adequately treated. The episode must significantly affect the patient’s ability to function professionally or socially or care for themselves (APA, 2022, pp. 113, 114). Obtaining a complete history is essential (Hany & Rizvi, 2024).

Schizophreniform Disorder

Manifestations of schizophreniform disorder are the same as those required to diagnose schizophrenia. The primary difference is the duration of symptoms (i.e., an episode of this disorder should persist for 1–6 months). During that time, there can be no (or minimal) concurrent periods of depressive or manic symptoms that would satisfy the requirements for schizoaffective disorder, MDD, or bipolar disorder with psychotic features (APA, 2022, pp. 111, 112).

With Peripartum Onset

The diagnostic criteria for a mood disorder with psychotic features and peripartum onset follow similar diagnostic guidelines as brief psychotic disorder with the specifier that symptoms occur during the final phase of pregnancy or within 4 weeks of delivery. Symptom onset is within the first 2 weeks after delivery in 65% of cases and can occur as early as the first 1–2 days postpartum. The presence of psychosis is the most severe of the peripartum mood disorders, but it is rare, affecting only 1 in 500–1,000 deliveries. Symptoms include auditory and visual hallucinations, paranoid or grandiose delusions, delirium or disorientation, impulsivity, poor judgment, abnormally elevated mood or energy levels, and depression. Impulsivity and poor judgment occur in 5% of individuals experiencing peripartum psychosis, increasing the risk of suicide or infanticide. Delusions are present in 50% of cases, and hallucinations occur in 25% of cases. Auditory hallucinations instructing the individual to kill their baby are rare but can occur in severe cases (APA, 2022, pp. 173, 174; Raza & Raza, 2023).

The affected individual may also believe that the child is possessed by the devil or an evil spirit or has special powers. Some individuals may become detached from their baby and stop providing care. In contrast, others may believe something is wrong with the baby and accuse family members or hospital staff of hurting or poisoning the baby. Symptoms typically start mild and progress in severity. Initially reported symptoms often include fatigue, insomnia, restlessness, emotional lability, and periods of crying. The postpartum individual may also report an inability to stand, walk, or move. Symptoms eventually progress to the individual experiencing suspiciousness, confusion, irrational thoughts, and incoherence. The individual may become obsessed with the baby’s health and well-being (APA, 2022, pp. 173, 174; Perry et al., 2021). There are different symptom profiles associated with peripartum psychosis:

• depression and/or anxiety occurs in 41% of individuals
• mania and/or agitation occurs in 34% of individuals
• atypical or mixed symptoms occur in 25% of patients (Toor et al., 2024)

Peripartum psychosis is commonly associated with a diagnosis of bipolar disorder. Among individuals diagnosed with bipolar disorder before pregnancy, the relapse rate is 32–62% during the postpartum stage. Peripartum psychosis has a good prognosis if symptoms are detected early and treated aggressively. It is considered a psychiatric emergency due to the risks to the patient and their baby; therefore, admission to an inpatient psychiatric facility is required. Treatment includes the use of typical and atypical antipsychotics and mood stabilizers. Unfortunately, these medications can pose a risk to the baby if the affected individual is breastfeeding. It is essential to educate the patient on the risks to the baby versus the benefits of treating the mental illness. Antidepressants should be used cautiously in these patients as they can trigger rapid cycling through manic and depressive states. Once an individual experiences peripartum psychosis, the recurrence rate in subsequent pregnancies is 30–50% (APA, 2022, pp. 173, 174; Conejo-Galindo et al., 2022; Raza & Raza, 2023).

Since peripartum mental health disorders, including peripartum psychosis, are often underdiagnosed, routine screening should be completed on discharge and at routine postpartum visits. The Edinburgh Postnatal Depression Scale and the Mood Disorder Questionnaire can aid HCPs in the early diagnosis of peripartum psychiatric disorders (American College of Obstetricians and Gynecologists [ACOG], 2023a).

Psychotic Disorder due to Another Medical Condition

This condition is characterized by significant delusions or hallucinations that lead to significant anguish or dysfunction (professionally, socially, academically). The patient’s test results, examination findings, and history indicate the symptoms are related to another medical condition and not more accurately attributed to delirium or another mental health condition (e.g., schizophrenia, acute stress disorder, brief psychotic disorder). The condition should be specified with delusions or hallucinations (APA, 2022, p. 131).

Substance-Induced Psychotic Disorder

To diagnose a patient with substance-induced psychotic disorder, at least one of the following symptoms must be present:

• illusions or perceived experiences that do not exist (sounds, voices, smells, visions, feelings, etc.)
• a misconception, belief, or thought that is firmly held despite not being grounded in reality (APA, 2022, pp. 126, 127)

Often, the patient’s symptoms become apparent during or after withdrawal or intoxication related to a substance or following a medication administration. The implicated substance must be known to cause the patient’s signs and symptoms. Symptoms cause substantial dysfunction in at least one environment (e.g., work, home, or social settings; APA, 2022, pp. 126, 127).

Medications to Treat Psychotic Disorders

While many treatment modalities are consistent throughout all psychotic disorders, there are unique treatments for each. Once an accurate diagnosis is determined, the patient’s safety is paramount. A determination of the best treatment setting is important. One patient may need inpatient care, while another may progress well in an outpatient setting. The treatment plan should be based on the presenting symptoms, the presence of a support system, socioeconomic stability, and whether the patient is a threat to themselves or others. The primary treatment for all psychotic disorders is a combination of pharmacotherapy and psychotherapy. Antipsychotic drugs, mood stabilizers, or antidepressants can be used in the treatment of psychotic disorders. Benzodiazepines may also be part of the treatment of peripartum psychosis or as acute treatment in emergencies. Individual and group psychotherapy can also be beneficial (Keshavan, 2025a).

Antipsychotic Drugs

Pharmacotherapy includes the management of the acute phase, followed by maintenance therapy, which strives to improve socialization, self-care, and mood. The rationale for maintenance treatment is to prevent relapse. Medication management aims to manage symptoms using the lowest effective dosage with the fewest side 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 within 5 years of the first acute episode, as this is the period in which most of the illness-related changes in the brain occur. Antipsychotic drugs, particularly atypical (or second-generation antipsychotics [SGAs]), are the first-line treatment for psychotic episodes and symptoms of agitation, delusions, and hallucinations. First-generation antipsychotics (FGAs) are also used as a treatment for psychotic disorders. Oral formulations are preferred, but intramuscular (IM) agents may be used during acute psychotic episodes (Freudenreich & McEvoy, 2025; Keshavan, 2025a).

First-Generation Antipsychotics

FGAs work by antagonizing dopamine D2 receptors. Some of the most common FGAs are chlorpromazine (Thorazine), haloperidol (Haldol), fluphenazine (Prolixin), loxapine (Loxitane), molindone (Moban), perphenazine (Trilafon), thioridazine (Mellaril), thiothixene (Navane), and trifluoperazine (Stelazine). FGAs pose the highest risk for extrapyramidal symptoms (EPS) among all antipsychotic medications. EPS are drug-induced movement disorders and are 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 and repetitive motions, agitation), and tardive dyskinesia (lip-smacking, worm-like tongue movements). Other less common side effects of FGAs include orthostasis, QT prolongation, weight gain, seizures, hyperlipidemia, and glucose abnormalities (D’Souza et al., 2025). Refer to Table 4 for a detailed overview of the special considerations of several FGAs.

Table 4

Common Types of FGAs

Medication	Special Considerations
Chlorpromazine (Thorazine)	IM injection should be administered to the upper outer quadrant of the gluteal area Requires a lower dose with IM than oral due to significant oral first-pass metabolism Use with caution in patients with hepatic or renal impairment
Haloperidol (Haldol)	Contraindicated in patients with severe toxic central nervous system depression or patients who are comatose Hypersensitivity can include anaphylaxis and angioedema
Fluphenazine (Prolixin)	IM dose should be 33–50% of the oral dose Use is contraindicated with hepatic impairment Use with caution in renal impairment
Loxapine (Loxitane) Loxapine (Adasuve) inhaler	Loxapine (Adasuve) inhaler is used to treat agitation and requires participation in the risk evaluation and mitigation strategy (REMS) program due to the risk of bronchospasm
Thioridazine (Mellaril)	Risk for dose-related QTc prolongation Obtaining a baseline ECG and serum potassium level is recommended, and use should be reserved for treatment failure of other antipsychotic drugs Use with caution in patients with hepatic impairment
Thiothixene (Navane)	Smoking may interfere with cytochrome P450 1A2 (CYP1A2), impairing drug bioavailability
Trifluoperazine (Stelazine)	Smoking may interfere with CYP1A2, impairing drug bioavailability Contraindicated in patients with hepatic disease

(APA, 2021; 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). Most SGAs work by antagonizing dopamine D2 and serotonin 5-HT2A receptors in the brain. Aripiprazole (Abilify), brexpiprazole (Rexulti), and cariprazine (Vraylar) function as partial dopamine and serotonin 5-HT1A agonists and 5-HT2A antagonists. Clozapine (Clozaril) also works differently, antagonizing alpha-adrenergic and cholinergic muscarinic receptors. EPS are less common with SGAs than with FGAs; however, EPS risk increases with SGA dose escalation. As a class, SGAs pose a greater risk for metabolic side effects, such as weight gain, hyperlipidemia, seizures, and diabetes mellitus (DM), which can contribute to the increased risk of cardiovascular mortality in patients diagnosed with schizophrenia. Less commonly, SGAs can cause orthostasis and QTc prolongation (D’Souza et al., 2025). Antipsychotic drugs should be avoided as a first-line treatment for delirium in older patients unless they are a threat to themselves or others. This is due to the increased risk of stroke and mortality in older adults with dementia and olanzapine (Zyprexa)-induced syncope (American Geriatrics Society, 2023). Refer to Table 5 for a detailed overview of the special considerations of common SGAs.

Table 5 

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 equating to at least 350 calories.
Olanzapine (Zyprexa)	IM administration is primarily utilized when the patient presents with severe agitation. When used for an acute episode, the recommended dose is 2.5–10 mg up to a maximum dose of 30 mg/day. Smokers may require a 30% greater daily dose than nonsmokers due to CYP1A2 induction. Females may need lower doses due to the increase in prolactin secretion that may occur. IM administration often requires a 40% dose reduction compared to the oral dose due to first-pass metabolism.
Risperidone (Risperdal)	Dose adjustment is required in patients with a creatinine clearance (CrCl) below 30 mL/min or severe hepatic impairment.
Cariprazine (Vraylar)	Use is not recommended in patients with severe hepatic impairment or those with renal impairment and a CrCl below 30 mL/min.
Clozapine (Clozaril)	Reserved for treatment-resistant schizophrenia, this only available is 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). It requires monitoring of ANC at baseline and frequent intervals (usually, weekly or biweekly); patients have an increased 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, 2021; 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 the presence of side effects is essential, as undesirable side effects are most commonly associated with treatment nonadherence and treatment discontinuation. Some side effects of treatment will improve over time, whereas others may worsen with dose escalation. In general, early in the course of treatment, the most common side effects include sedation, fatigue, orthostatic hypotension, and anticholinergic effects such as dry mouth, constipation, and difficulty urinating. As treatment progresses, many of these side effects dissipate or improve. In contrast, side effects corresponding with metabolic syndrome (e.g., weight gain, hyperlipidemia, and 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, which can include loss of libido, anorgasmia, erectile dysfunction, and ejaculatory disturbances such as retrograde ejaculation (APA, 2021).

FGAs and SGAs are available in short-acting/IR and ER oral formulations and 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, clinicians are advised to determine the etiology of the patient’s nonadherence with oral treatment before changing to LAI. If nonadherence is related to undesirable adverse effects of oral treatment, the patient should trial an alternative oral medication before transitioning to LAI. Symptoms of agitation and hallucinations typically resolve first (within days), but delusions may take weeks to resolve, and full effects are usually occur within 6 weeks; some antipsychotic medications require strict monitoring as outlined by the US Food and Drug Administration (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 medication as described within the FDA-approved prescribing information through the heightened monitoring and surveillance of patients receiving these medications (APA, 2021; FDA, 2021; National Institute of Mental Health [NIMH], 2023).

When antipsychotic medications are utilized, providers must monitor patients for physical and laboratory changes resulting from treatment (APA, 2021). Patients taking SGAs should undergo the following monitoring parameters at baseline and follow-up visits, as specified:

• personal and family history of obesity, DM, hyperlipidemia, hypertension, or cardiovascular disease should be assessed before initiating treatment and then annually
• weight, height, and body mass index (BMI) should be assessed before treatment, at every follow-up visit for 6 months, and then at least every 3 months
• fasting blood glucose or HbA1c should be assessed before treatment, at 4 months after treatment initiation, and then annually
• fasting lipid profile should be assessed before treatment, at 4 months after treatment initiation, and then annually
• depending on which antipsychotic is prescribed, an ECG should be performed before initiating treatment and repeated with each dose change
• Clozapine (Clozaril) requires ANC monitoring weekly for the first 6 months, then every 2 weeks from months 6–12, and then monthly after 12 months if counts remain stable (APA, 2021)

Mood Stabilizers

Mood stabilizers decrease manic and hypomanic symptoms that may occur during psychotic episodes or with schizoaffective disorder of the bipolar type. While significant evidence does not support using these medications as monotherapy for psychotic disorders, there is ongoing support for their use as adjunctive therapies to manage the symptoms and potential comorbidities of psychotic disorders. Mood stabilizers work to stabilize the manic highs and depressive lows of mood disorders. Lithium (Lithobid), a commonly prescribed mood stabilizer that works by altering sodium transport across neurons, is used off-label to treat symptoms in psychotic disorders, including schizophrenia. There is moderate concern about long-term safety and tolerability with lithium (Lithobid) use, which is considered possibly hazardous in breastfeeding individuals (Chen et al., 2023; NIMH, 2023).

Alternatives for mood stabilization include antiseizure medications such as divalproex sodium (Depakote), valproic acid (Depakene), carbamazepine (Tegretol), and lamotrigine (Lamictal). Divalproex sodium (Depakote) is the first-line monotherapy for acute mania and maintenance therapy of bipolar disorder based on level 1 evidence. Carbamazepine (Tegretol) is considered a second-line treatment for acute mania based on level 1 evidence and can be used for maintenance treatment. Lamotrigine (Lamictal) is not recommended for acute mania. 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. Mood stabilizers are associated with several adverse effects, including itching, a rash, excessive thirst, frequent urination, tremors, nausea, vomiting, slurred speech, tachycardia, bradycardia, loss of consciousness, changes in vision, seizures, hallucinations, loss of coordination, and swelling of the eyes, face, lips, tongue, throat, hands, feet, ankles, or lower legs (Chen et al., 2023; NIMH, 2023).

In those with a psychotic disorder with depressive features, symptoms can be improved with the adjunctive use of antidepressants. This is particularly true with schizoaffective disorder and peripartum psychosis. Depression may be the underlying mood disorder that leads to psychotic symptoms. Most FDA-approved antidepressants target the three neurotransmitters traditionally associated with depression: serotonin, norepinephrine, and dopamine. These antidepressants usually take at least 2–4 weeks to reach therapeutic levels. Symptoms such as sleep disturbances, appetite changes, and difficulty concentrating often improve before a notable change in mood occurs. Due to their side effect profiles, most antidepressants need to be tapered up slowly when starting therapy and tapered down gradually when discontinuing treatment. If stopped abruptly, some antidepressants pose a risk for withdrawal-like symptoms such as dizziness, headaches, flu-like syndrome (tiredness, chills, muscle aches), agitation, irritability, insomnia, nightmares, diarrhea, and nausea. Contemporary obstetric guidance emphasizes individualized risk-benefit discussions when considering antidepressant use in individuals of childbearing age (NIMH, 2023).

In 2004, the FDA required a 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 extended a few years later to include all young adults, especially those under 25, stating that these individuals may experience an increase in suicidal thoughts or behaviors during the first few weeks of treatment and warning clinicians to monitor patients for this effect. The FDA also requires manufacturers to provide a Patient Medication Guide (MedGuide), which is given to patients receiving these medications to advise them of the risks and precautions that can be taken to reduce the risk of suicide. Further, clinicians are advised to screen patients for risk of suicide before prescribing antidepressants (FDA, 2018). Table 6 outlines the points that must be included in the boxed warning.

Table 6

FDA Antidepressants Boxed Warning Points

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

Anyone considering the use of an antidepressant in a child or adolescent for any clinical use 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 HCP if any changes occur.

Each drug requires a statement regarding whether the particular drug is approved for any pediatric indication(s) and, if so, which one(s).

 (FDA, 2018)

Selective serotonin reuptake inhibitors (SSRIs) are typically the safest initial antidepressant choice, the most well tolerated, and the preferred antidepressant to treat psychotic disorders with depressive symptoms. SSRIs include drugs such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac), fluvoxamine (Luvox CR), paroxetine (Paxil), and sertraline (Zoloft). SSRIs can increase the levels of serotonin in the body, posing a risk for serotonin syndrome, which is a condition characterized by agitation, anxiety, confusion, high fever, sweating, tremors, lack of coordination, dangerous fluctuations in blood pressure, and rapid heart rate. Serotonin syndrome is a potentially life-threatening condition for which patients must seek immediate medical attention. Adverse effects of SSRIs include nausea, vomiting, diarrhea, headaches, dizziness, dry mouth, drowsiness, insomnia, nervousness, agitation, restlessness, sexual dysfunction, and changes in appetite leading to anorexia or weight gain. SSRIs should not be discontinued abruptly due to the risk of withdrawal symptoms. Patients should not take an SSRI within 14 days of treatment with a monoamine oxidase inhibitor (MAOI; Woods, 2023).

Regarding pharmacological therapy for the treatment of anxiety, benzodiazepines are among the most commonly used medications for the immediate and short-term relief of acute symptoms. Benzodiazepines work by enhancing the effects of gamma-aminobutyric acid (GABA) in the brain and can be used as the first-line option for general anxiety disorder but are considered a second-line treatment for panic disorder and social anxiety disorder behind antidepressants. 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). These agents are also frequently used for short-term anxiety management for minor medical procedures. While benzodiazepines have the advantage of a quick onset of action and are highly effective in alleviating acute symptoms, they are Schedule IV controlled substances, according to the US Drug Enforcement Administration (DEA). Benzodiazepines also carry a high risk of tolerance and can cause withdrawal symptoms if abruptly discontinued, so they should be tapered slowly and carefully. Additional adverse effects of benzodiazepines include drowsiness or tiredness, dizziness, nausea, blurred vision, headaches, confusion, and nightmares. For these reasons, benzodiazepines are often considered second-line options for chronic anxiety—behind antidepressants—or used on an as-needed basis for breakthrough symptoms. The FDA previously categorized most benzodiazepines as pregnancy category D or X (positive evidence of risk); therefore, individuals of childbearing age should be counseled extensively on their risk before starting a benzodiazepine. The most recent version of the American Geriatrics Society Beers Criteria recommends that benzodiazepines be avoided in older patients for the treatment of insomnia, agitation, or delirium due to an increased risk of falls and high rate of physical dependence, especially longer-acting versions (American Geriatrics Society, 2023; NIMH, 2023; Woods, 2023).

Buspirone (Buspar) is approved for the treatment of chronic anxiety, but it has the potential to be used in the treatment of schizophrenia. It is not a benzodiazepine or a controlled substance; it works by binding to serotonin and dopamine D2 receptors. Unfortunately, it does not work for everyone and needs to be taken every day as it is ineffective when taken on an as-needed basis. Adverse effects of buspirone (Buspar) include dizziness, headaches, nausea, nervousness, lightheadedness, excitement, and difficulty sleeping. The FDA previously categorized Buspirone (Buspar) as pregnancy category B (no evidence of risk). Beta-blockers can alleviate the physical symptoms of anxiety, such as sweating, trembling, and tachycardia, during especially stressful events, such as large social gatherings, weddings, or public speaking engagements. They can be taken as needed but can cause hypotension, bradycardia, dizziness, weakness, fatigue, and cold hands and are not recommended for patients with diabetes or asthma (NIMH, 2023).

Treatment by Disorder

Brief Psychotic Disorder

Psychotherapy for brief psychotic disorder includes informing the patient and their family, friends, or loved ones about the diagnosis and treatment options. This condition disrupts the daily functioning of the individual’s life and those around them, and reintegration into their social milieu is crucial. The treatment plan should include the management of comorbid disorders and stressors and the development of new coping skills. Ongoing monitoring of both pharmacotherapy and psychotherapy should be long-term for successful management and early recognition of relapses (Stephen & Lui, 2023).

Antipsychotics are the first-line treatment for brief psychotic disorder. SGAs, including quetiapine (Seroquel), paliperidone (Invega), olanzapine (Zyprexa), risperidone (Risperdal), aripiprazole (Abilify), and ziprasidone (Geodon) are utilized more frequently than FGAs due to the decreased prevalence of EPS. FGAs—including haloperidol (Haldol), chlorpromazine (Thorazine), and perphenazine (Trilafon)—are utilized when treatment with an SGA is contraindicated or ineffective. Although the symptoms of brief psychotic disorder go into remission in less than 1 month, it is recommended that treatment continue for 1–3 months after symptoms disappear. Anticholinergics such as benztropine (Cogentin) can be used to lessen the severity of EPS. Benzodiazepines such as alprazolam (Xanax) or lorazepam (Ativan) can be effective when used to treat acute agitation and combativeness (Stephen & Lui, 2023).

 

Delusional Disorder

Since there is limited patient insight into this disorder, individuals face difficulties finding an effective treatment. Developing a solid relationship with a trusted HCP is paramount for success. Hospitalization is not typically needed. Treatment includes psychotherapy and pharmacological treatment. Psychotherapy focuses on building a therapeutic partnership between the patient and their HCP. Pharmacological treatment of delusional disorder includes the use of antipsychotics. The patient’s history of medication adherence may be a factor in determining which antipsychotic is the best choice. Antipsychotics should be started for a minimum trial period of 6 weeks with a subsequent evaluation of effectiveness. It is recommended that treatment begins at a low dose with titration as needed for symptom management. After 6 weeks, an alternative drug class can be considered until treatment goals are achieved. If monotherapy with antipsychotics does not alleviate symptoms, medications such as lithium (Lithobid), valproic acid (Depakene), or carbamazepine (Tegretol) can be used as adjunct therapy. Adherence may decrease with increased complexity of the treatment regimen. Combination psychotherapy and pharmacotherapy provide the best treatment response (Joseph & Siddiqui, 2023).

 

Schizoaffective Disorder

Schizoaffective disorder responds best to a combination of pharmacotherapy, psychotherapy, and life skills training. The treatment will vary based on whether the disorder is of the depressive or bipolar (manic) type. Hospitalization may be needed initially, and long-term treatment is required to manage ongoing symptoms. Psychotherapy can be individual or group therapy. Group therapy may involve the entire family, as this disorder impacts relationships and can cause family suffering. Both the individual and their family need an understanding of the disorder and the treatment plan. The individual needs to build a trusting relationship with their HCP during individual therapy. The family learns how to provide reality checks for the patient during psychotic episodes, facilitate appropriate medication management, and develop better social skills for the individual and their family (Keshavan, 2025b).

The recommended treatment for the bipolar (manic) type of schizoaffective disorder is an SGA as monotherapy. This may alleviate symptoms; however, if symptoms persist, lithium (Lithobid), carbamazepine (Tegretol), or valproate (Depakote) may be added. To treat the depressive type, an SGA is the first-line treatment until positive symptoms are well managed. If depressive symptoms continue, an antidepressant can be initiated. Antidepressants can help manage feelings of hopelessness and sadness and improve sleep patterns; the preferred class of antidepressants is SSRIs. The only FDA-approved antipsychotic for schizoaffective disorder is paliperidone (Invega). However, HCPs may utilize other SGAs to treat schizoaffective disorder (Keshavan, 2025b).

 

Schizophrenia

Treatment for schizophrenia is multifactorial and lifelong and includes pharmacological management in combination with psychosocial support. A psychiatrist usually guides treatment, and due to the complexity of the diagnosis, coordinated specialty care (CSC) is recommended. CSC refers to a team approach involving case managers, family, and social workers, in addition to educational and employment service involvement. CSC is beneficial for patients with schizophrenia in reducing symptoms, improving quality of life, increasing adherence with medication therapy, and enhancing outcomes. Electroconvulsive therapy (ECT) is a treatment recognized as beneficial to patients with psychosis related to schizophrenia that is unresponsive to pharmacotherapy. According to the APA, ECT as an adjunct therapy with antipsychotics increases the rate of remission. ECT is also beneficial when initiated for patients who require emergent treatment or those with an increased risk of suicide (APA, 2021; NIMH, 2023).

According to the APA (2021) practice guidelines for treating patients with schizophrenia, SGAs are considered first-line treatment. While the selection of the type of antipsychotic agent depends on various individual patient factors, SGAs are generally preferred over FGAs due to their superior side-effect 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 utilizing one antipsychotic over another, except for clozapine (Clozaril). Clozapine (Clozaril) is the only SGA that is not recommended as first-line treatment, as it carries a risk for life-threatening agranulocytosis (refer to Table 5). Clozapine (Clozaril) is reserved for patients whose symptoms are resistant to treatment with other antipsychotic drugs, as it is considered the most effective antipsychotic drug for managing treatment-resistant schizophrenia (APA, 2021; Freudenreich & McEvoy, 2025).

 

Schizophreniform Disorder

As schizophreniform disorder is a short-term version of schizophrenia, it is treated similarly. The goal of treatment is to stabilize and protect the patient from harm. Hospitalization may be needed based on patient presentation and the severity of symptoms. Individuals who are likely to cause harm to themselves or others must be treated more aggressively, as with all psychotic disorders. This disorder responds best to psychotherapy and pharmacotherapy, and individual therapy and group therapy are indicated. Medications to treat the psychotic symptoms of schizophreniform disorders consist of antipsychotics, including risperidone (Risperdal), quetiapine (Seroquel), or ziprasidone (Geodon). Once symptoms improve and the patient returns to baseline, pharmaceutical treatment should continue for at least 12 months and then be tapered. During this time, the patient should be monitored closely for signs of symptom relapse (Keshavan, 2025c).

 

Psychosis with Peripartum Onset

Timely identification is vital with peripartum psychosis, as the safety of both the patient and their baby is at risk. In most cases, immediate hospitalization and separation from the infant are required. Mood stabilizers, SGAs, and benzodiazepines may be used to treat the psychosis. The mood stabilizer lithium (Lithobid) is considered the gold standard for treating peripartum psychosis. Other mood stabilizers that can be used include carbamazepine (Tegretol) and divalproex sodium (Depakote). SGAs, including quetiapine (Seroquel) or olanzapine (Zyprexa), and benzodiazepines such as lorazepam (Ativan) or alprazolam (Xanax) can also be used. SSRIs such as sertraline (Zoloft) and paroxetine (Paxil), mood stabilizers such as carbamazepine (Tegretol), valproic acid (Depakene), and short-acting benzodiazepines such as lorazepam (Ativan) or alprazolam (Xanax) are considered moderately safe during breastfeeding. However, breastfeeding is questionable for an individual suffering from psychosis with peripartum onset since it can lead to insomnia and exhaustion, which can further exacerbate mental health conditions. Lithium (Lithobid) should be used with extreme caution and extensive monitoring while breastfeeding as it may cause toxicity in infants. If lithium (Lithobid) is used, standards of care include monitoring serum drug levels and thyroid and renal function of parent and infant during therapy. HCPs should also monitor adherence and effectiveness of treatment (ACOG, 2023b; Raza & Raza, 2023).

Adjunctives to pharmacotherapy are psychotherapies. Treatment requires social support, psychoeducation, and psychotherapy for the entire family and support system for optimal recovery. Individual psychotherapy for patients can help with the transition to parenthood. The demands and apprehensions regarding the new role can increase anxiety and negative emotions. Individual psychotherapy can help reduce depressive symptoms and improve the adjustment to parenting. Providing reassurance and emotional support can boost the patient’s self-esteem and increase their confidence as a parent. Group psychotherapy may also be beneficial to help the patient and family share their experiences with others. The treatment plan should be created collaboratively with the patient, their family, and the health care team to determine the best path forward for each patient. ECT is further considered safe and effective, with few complications, in postpartum patients with a relapse or exacerbation of psychosis (ACOG, 2023b).

Psychotic Disorder due to Another Medical Condition

Identifying and correcting the underlying medical cause of the psychosis reduces or eliminates symptoms of this condition. If symptoms remain following correction of the medical cause, or the underlying cause is not correctable, the psychotic symptoms should be treated using an antipsychotic as described previously (Keshavan, 2025d).

Substance-Induced Psychotic Disorder

Treatment of substance-induced psychotic disorder is specific to the aggravating factor. If the psychosis results from administering a substance or medication, discontinuing use and administering an anxiolytic or antipsychotic are sufficient to alleviate symptoms. Antipsychotics are the first-line treatment for a psychotic episode induced by a dopamine-stimulating substance (e.g., amphetamines). For some substances (e.g., lysergic acid diethylamide [LSD]), once the individual can spend time in a quiet environment with minimal external stimuli, the psychotic episode typically resolves (Keshavan, 2025e).

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