At the conclusion of this exercise, the APRN will be prepared to:
- Identify the appropriate terms and definitions related to psychotic disorders.
- Consider the impact of psychotic disorders on healthcare in the US.
- Identify possible risk factors that influence the development of psychotic disorders.
- Reference appropriate tests and evaluations used to diagnose psychotic disorders.
- Consider differential diagnoses for psychotic disorders.
- Discuss treatment interventions for individuals diagnosed with psychotic disorders.
Psychotic disorders include several serious illnesses affecting the mind. An individual suffering from a psychotic disorder will have difficulty thinking clearly, poor judgment, inappropriate emotional responses, inability to communicate effectively, inability to understand reality, or inability to behave appropriately in daily life. In severe cases, those with a psychotic disorder will have trouble orienting to reality and managing daily life. The different types of psychotic disorders include schizophrenia (the most common form of psychosis), schizoaffective disorder, schizophreniform disorder, brief psychotic disorder, delusional disorder, shared psychotic disorder, substance-induced psychotic disorder, psychotic disorder due to another condition such as a head injury or brain tumor, paraphrenia, or postpartum psychosis (Shiel, 2018). Below is a summary of the overarching characteristics of each of these conditions.
Brief psychotic disorder is 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. Recovery from a brief psychotic disorder typically occurs within one month of symptom onset (American Psychiatric Association, [APA], 2013).
Schizophrenia includes behavioral features such as delusions and hallucinations lasting longer than six months (APA, 2013).
Schizoaffective disorder includes both schizophrenia symptoms and a mood disorder such as depression or mania (APA, 2013).
Schizophreniform disorder includes symptoms of schizophrenia lasting at least one month but no more than six months (APA, 2013).
Substance-induced psychotic disorder is hallucinations or delusions caused by drug withdrawal from hallucinogens such as crack cocaine, amphetamine, methamphetamine, alcohol, or cannabis (APA, 2013).
Postpartum psychosis occurs within one to three months after delivery and includes hallucinations and/or delusions that can lead to suicide or injury to others, including the newborn (Shiel, 2018).
Psychosis is used to describe conditions affecting the mind that cause a loss of reality in the individual. During psychosis, there may delusions and hallucinations. Additionally, there may be incoherent or nonsensible speech or inappropriate behavior. During a psychotic episode, one can experience depression, anxiety, social withdrawal, sleep disturbances, and difficulty with overall functioning (National Institute of Mental Health [NIMH], n.d.).
Delusions are false beliefs (NIMH, n.d.).
Hallucinations are seeing or hearing things that other people do not see (NIMH, n.d.).
Paraphrenia symptoms include those similar to schizophrenia and start later in life, such as the elderly (APA, 2013).
Impact of Psychotic Disorders
Approximately 1% of the population suffers from a psychotic disorder, which generally appears in the late teenage years to the early 30s, and men and women are impacted equally. The most common psychotic disorder is schizophrenia. According to the World Health Organization (WHO), there are approximately 20 million people affected by schizophrenia worldwide. 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 (WHO, 2019). Homeless adults have a high incidence of schizophrenia and psychotic disorders secondary to the inability to maintain employment or make appropriate decisions related to their living conditions. There are as many as 100 million people globally that are considered homeless, and over 1.6 billion lack adequate housing. In a systematic review by Ayano et al. (2019) on mental illness among the homeless, approximately 25-50% of the homeless were found to have psychiatric disorders of various types. Prevalence estimates within this study found up to 60% of the homeless with psychiatric disorders suffer from schizophrenia. Schizophrenia and other psychotic disorders are associated with a high level of disability, drug abuse, alcohol abuse, or suicide. Psychotic disorders negatively impact not only the individual that is suffering from the disorder, but also their family members and loved ones (Ayano et al., 2019).
Psychotic disorders have a genetic component, and individuals who have a family member with a psychotic disorder are more likely to develop one than those without a family history. Psychotic disorders may be caused by an over-activity of brain chemicals that are necessary for normal functioning. A brain injury during fetal development or childhood also increases the risk of developing a psychotic disorder (Psychguides, 2020). Table 1 identifies risk factors for each type of psychotic disorder.
Type of Disorder
Brief psychotic disorder
(Sadock et al., 2014)
While each type of psychotic disorder has unique diagnostic criteria, there are similarities among them as a group. Consistent symptoms among each of the diagnoses are delusions, paranoia, visual or auditory hallucinations, and a general decline in the individual's ability to make decisions (Psychguides, 2020).
Brief Psychotic Disorder
The Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM 5) requires the presence of one or more of the following symptoms:
- Disorganized speech
- Grossly disorganized or catatonic behavior
Additionally, the duration of an episode must be at least one day but less than one month with a return to previous levels of function. The disturbance cannot be better explained by major depressive disorder (MDD) or bipolar disorder with psychotic features or another psychotic disorder such as schizophrenia and is not attributed to substance abuse or some other medical condition (APA, 2013).
Differential diagnoses include:
- Psychotic disorder with medical causation
- Psychotic affective disorder
- Schizophrenia-spectrum disorders
- Personality disorders
- Delusional disorder
- Substance abuse withdrawal
- Substance-induced psychosis
If a major mood component exists in addition to the brief psychotic disorder as previously described, then psychotic affective disorder is diagnosed. However, even in the presence of treatment, patients with 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 the presence of symptoms longer than 30 days. Those with a personality disorder such as borderline personality disorder may have episodic incidents of psychosis that are 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 complete history and physical along with laboratory testing and/or imaging can help to reveal the causal condition (Stephen & Lui, 2019).
The patient with suspected brief psychotic disorder needs a complete history and physical. A review of recent stressors should be considered, including the death of family or friends, military activity, environmental disasters, or recent immigration. The presenting symptoms of brief psychotic disorder can mimic delirium and may be severe. Labs can aid in ruling out other disease processes, yet there are no specific diagnostic labs that would define brief psychotic disorder. Suggested labs include a serum pregnancy test, complete blood count (CBC), toxicology screening (alcohol, methamphetamines, cannabis, opium, heroin/morphine, or tobacco), electrolyte levels, liver function tests, thyroid function tests, glucose level, and urinalysis. An electrocardiogram (ECG) in addition to a computer tomography (CT) or magnetic resonance imaging (MRI) of the head may be indicated to evaluate for structural or underlying conditions causing the symptoms (Stephen & Lui, 2019).
The diagnosis of delusional disorder is based on one or more delusional thoughts that persist for a month or longer with no other explanation, such as physiological, other mental health conditions, medical condition, or substance abuse. An individual's cultural beliefs should be considered in diagnosing delusional disorder, as this can influence the content of the delusion (Joseph & Siddiqui, 2019).
DSM 5 diagnostic guidelines for delusional disorder include delusions without the following:
- No prominent hallucinations, either auditory or visual
- No significant flattening of affect
- No thought disorder
- Psychosocial functioning is not impaired markedly
- No odd or bizarre behavior noted
- Delusions have lasted longer than associated depression or mania (APA, 2013).
Frequent types of delusions could include:
- Delusional jealousy- believing that one’s sexual partner is unfaithful
- Bizarre- delusion that is impossible, unrelated to normal life, and not understandable
- Erotomaniac-delusion that someone of higher status such as a movie star is in love with the individual
- Grandiose- delusion that the individual has a great talent, power, knowledge, or inflated self-worth
- Persecutory- delusion that others are harassing, attacking, conspiring against, or obstructing the individual’s pursuit of long-term goals
- Somatic- involve bodily functions and sensations
- Mixed- combination of various types of delusions
- Thought broadcasting- delusion that one’s thoughts are being projected and perceived by others
- Thought insertion- delusion that the individual’s thoughts are not their own but being placed in their mind by others (APA, 2013).
An individual with delusional disorder’s functionality is not impaired outside their delusion and they are usually stable otherwise (exhibiting baseline or normal behavior). They are usually hypersensitive with ego defense mechanisms like projection (putting undesirable feelings or emotions onto someone else, rather than dealing with them), denial (refusing to admit to yourself that something is real), or reaction formation (unacceptable or threatening unconscious impulses are denied and replaced in consciousness with their opposite; APA, 2013). When social isolation, distrust, low self-esteem, suspicion, or envy become unbearable, the individual may seek an explanation and form a delusion as the solution to these factors (Joseph & Siddiqui, 2019).
Differential diagnoses include:
- Obsessive-compulsive disorder (OCD)
- Schizophreniform disorder
- Delirium/major neurocognitive disorder
- Bipolar disorder
For individuals who are convinced their obsessions and compulsions are true convictions, the diagnosis of OCD with absent insight is appropriate. The active phase of schizophrenia can be differentiated from delusional disorder by the presence of other symptoms, including but not limited to hallucinations, both auditory and visual. Delirium/major neurocognitive disorder mimics delusional disorder but can be distinguished through the symptom manifestation timeline. With depression or bipolar disorder, delusions occur with mood episodes, yet with delusional disorder, the span of delusions exceeds the total duration of the mood symptoms (Joseph & Siddiqui, 2019).
DSM 5 diagnostic guidelines include:
- An uninterrupted period of illness during which there is a major depressive episode, a manic episode, or a mixed episode concurrent with symptoms that meet the criterion for schizophrenia (delusions, hallucinations, disorganized speech, grossly disorganized or catatonic behavior, or flat affect)
- Delusions or hallucinations present for at least two weeks in the absence of prominent mood symptoms for the same period of illness.
- Symptoms for a mood episode are present for a major portion of the total duration of the active and residual periods of the current illness.
- The disturbance is not due to the direct physiological effects of a substance or general medical condition (APA, 2013).
Schizoaffective disorder is a frequently misdiagnosed psychiatric disorder in clinical practice. Some researchers have considered removing the diagnosis from the DSM 5 as a diagnosis altogether. Since the disorder is part of a spectrum sharing criteria from other psychiatric disorders, it can be a challenge to properly diagnose. 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. Wy and Saadabadi (2020) note that investigation of the possible causes of mood disorders and schizophrenia as separate disorders might be appropriate in developing a diagnosis since studies show that as high as 50% of those with schizophrenia may also have depression. Mood disorders and schizophrenia have correlated risk factors, thus increasing the risk of two different diagnoses or the single diagnosis of schizoaffective disorder. During the diagnostic workup, a thorough history and physical must be completed, including a mental status examination and neurological examination to evaluate for other diagnoses. Further evaluation can be completed as with other disorders, including the following:
- Lipid Panel
- Urine drug screen
- Urine pregnancy test
- Thyroid panel
- Rapid plasma reagent
- HIV test
- MRI or CT to evaluate for suspected intracranial abnormalities should be considered (Wy & Saadabadi, 2020).
Differential diagnoses include:
- MDD with psychotic features
- Bipolar disorder
For a schizoaffective disorder diagnosis, there must be at least two weeks of only psychotic symptoms, including delusions or hallucinations, without mood symptoms. Otherwise, the majority of the illness period includes a major mood episode of depression or mania. If the psychotic symptoms are predominant during the majority of the illness, it is more likely that schizophrenia exists. Schizophrenia further requires six months of prodromal or residual symptoms, which schizoaffective disorder does not. Patients with MDD with psychotic features only have psychotic features during their mood episodes and not at other times. Finally, bipolar disorder patients should only experience psychotic features during their manic episode(s) which differs from the expectation for schizoaffective disorder (Wy & Saadabadi, 2020).
The DSM 5 diagnostic criteria for schizophrenia include:
- Characteristic symptoms of two or more of the following: delusions, hallucinations, disorganized speech, grossly disorganized or catatonic behavior, or negative symptoms (diminished emotional expression) present for a major portion of time during one month
- Social/occupational dysfunction, including work, interpersonal relations, or self-care that is markedly below the baseline
- The duration of illness/symptoms is at least six months
- Schizoaffective disorder and mood disorder with psychotic features have been ruled out either because of no major depressive, manic, or mixed episodes have occurred simultaneously with the active phase symptoms or if the mood episodes have occurred during active-phase symptoms, their total duration has been brief relative to the duration of the active and residual period
- The disturbance is not related to the direct physiological effects of substance abuse or a general medical condition.
- The disturbance is not related to a history of autistic disorder or other developmental disorders, schizophrenia is only diagnosed if the delusions or hallucinations last for at least a month (APA, 2013).
Multiple studies identify 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, it is important to perform a thorough history and physical. Cannabis use is associated with psychosis and should be considered during history taking (Hany et al., 2019). Substance abuse correlates with but does not cause schizophrenia; people with schizophrenia abuse alcohol and drugs more frequently than the general population. Women experience more mood symptoms than men (Sadock et al., 2014). A thorough review of systems should be completed, including the following laboratory or diagnostic tests:
- Urea and electrolytes (electrolyte imbalance leading to delirium can be ruled out),
- Serum calcium (hypo- or hyperthyroidism can have psychiatric manifestations),
- Blood glucose level (confusion can be related to hypo-hyperglycemia),
- Thyroid function tests (hypothyroidism and subsequent depression can present with psychotic features; severe hyperthyroidism can cause mental status changes),
- 24-hour cortisol level (Cushing’s and Addison’s disease can present with psychiatric components),
- 24-hour catecholamine/5-HIAA collection (to evaluate for pheochromocytoma/carcinoid syndrome),
- CT or MRI of the head (evaluate for any impairment or structural abnormality), and/or
- HIV/syphilis serology (both can cause significant psychiatric symptoms).
Differential diagnoses include:
- Psychosis secondary to organic causes
- Schizoaffective disorder
- Schizophreniform disorder
- Pervasive developmental disorder
- Paranoid personality disorder
- Sleep-related disorders
- Delusional disorders
- Mood disorders with psychotic features
- Substance-induced psychotic disorder (Hany et al., 2019).
Ruling out other mental health disorders is a significant part of diagnosing schizophrenia. A risk assessment should be done regarding harm to others or self. Since the initial signs of schizophrenia usually arise in adolescence or early adulthood, insight may be lacking; thus, family and friends are a great source of data to help determine the appropriate diagnosis. Early in the disease process, it is not uncommon for relatives to report personality changes or unusual behaviors, suicide attempts, altercations with law enforcement, or even referrals for mental health services from the justice system. Screening tools such as the Criteria of Prodromal Syndromes (COPS), Structured Interview for Prodromal Syndromes (SIPS), or Personal Assessment and Crisis Evaluation Clinic (PACE) may facilitate the detection of schizophrenia in premorbid states (Hany et al., 2019).
The DSM 5 diagnostic guidelines require that two or more of the following are present for a significant portion of time during a single month:
- Disorganized speech
- Grossly disorganized or catatonic behavior
- Negative symptoms such as diminished emotional expression (APA, 2013)
Additionally, the guidelines for diagnosis include:
- An episode of the disorder, including prodromal, active, and residual phases lasting at least one month but less than six months.
- Substance abuse and general medical conditions should be excluded to make a diagnosis of schizophreniform disorder.
- Schizoaffective disorder and mood disorder with psychotic features have been ruled out (APA, 2013).
Other mental health conditions that should be ruled out include delusional disorder, autism spectrum disorder, attention deficit hyperactivity disorder, OCD, traumatic brain injury, or post-traumatic stress disorder.
Differential diagnoses include:
- Brief psychotic disorder
- Bipolar affective disorder
- Schizoaffective disorder
- Schizophrenia (Bhalla, 2018).
The DSM 5 diagnostic criteria include the diagnostic criteria for a brief psychotic disorder along with the specifier "with postpartum onset" if the onset is during the final phase of pregnancy or within four weeks postpartum (APA, 2013). Onset is within the first two weeks after delivery in 65% of the cases and can occur within the first one to two days. Symptoms include elated, dysphoric, or labile mood, agitation, or bizarre behaviors. Psychotic symptoms include delusions such as the baby being harmed, delusions of control, or command hallucinations. Thought processes are typically disorganized, and the patient may be confused, perplexed, or have olfactory or tactile hallucinations. The mother and baby are both at risk for harm. There is an abrupt onset following childbirth that may have multiple pathophysiological components. The birth of the baby brings changes to the individual and their family. Hormonal changes are occurring rapidly, including a drop in gonadal steroids; serotonin and dopamine are affected by the estrogen changes leading to further mood disturbances. Sleep disruption is a potential factor and may lead to autoimmune dysfunction and immune system dysregulation leading to altered mental status (Monzon et al., 2014).
Differential diagnoses include:
- Primary cerebral or systemic disease such as eclampsia or infection
- Exogenous toxic substance or hormones
- Baby blues (maternal mood swings from elation to crying, irritability, anxiety, and insomnia, but the care of the baby is not impaired)
- Postpartum depression (similar symptoms to baby blues but the care of the baby may be suboptimal leading to negative consequences on mother and baby) (Rai et al., 2015).
Since postpartum mental health disorders, including postpartum psychosis, are often underdiagnosed, routine screening should be completed on discharge and routine postpartum visits. The Edinburgh Postnatal Depression Scale and the Mood Disorder Questionnaire can aid healthcare providers in the early diagnosis of postpartum psychiatric disorders. The following diagnostic or laboratory tests should be done to identify or evaluate for other conditions:
- Blood urea nitrogen
- Serum glucose
- Vitamin B12
- Thyroid function tests
- Urinalysis and urine culture in the presence of fever
- Urine drug screen
- CT or MRI to evaluate for stroke, hemorrhage, or aneurysm (Rai et al., 2015).
Additionally, there are psychotic disorders due to medical conditions, substance-induced psychotic disorders, and psychotic disorder not otherwise specified as DSM 5 diagnoses. Each has some component of delusions and hallucinations, along with mood or behavioral characteristics. With each, there is impairment of social, occupational, or other important areas of functioning (APA, 2013). Paraphrenia is not included in the DSM 5, but the term is still occasionally used to identify those with atypical psychoses, delusional disorder, or other schizoaffective disorders in older adults (Cecato, 2018).
Treatment of Psychotic Disorders
While many treatment modalities are consistent through all psychotic disorders, there are unique treatments for each. Broadly, once an accurate diagnosis has been determined, the patient’s safety is of paramount concern. A determination of treatment setting is important. Some may need inpatient care while others may progress well in the outpatient setting. Treatment decisions should be based on the presenting symptoms, presence of a support system with family or friends, socioeconomic stability, but most of all, whether the patient is a threat to themselves or others. The primary treatment for all psychotic disorders is a combination of pharmacotherapy and psychotherapy. A combination of antipsychotic drugs, mood stabilizers, and/or antidepressants can be used in the treatment of most psychotic disorders. Benzodiazepines may also be part of the treatment of postpartum psychosis or as acute treatment in emergencies. Individual and group psychotherapy can be beneficial, as well (PsychGuides, 2020).
Pharmacotherapy includes 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. The goal of medication use is to manage signs and symptoms using the lowest effective dosage with the least amount of side effects possible. Prompt initiation of medication therapy within five years of the first acute episode is recommended; this is the period in which most of the illness-related changes in the brain occur. 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. It can take several weeks to notice an improvement in symptoms (Freudenreich & McEvoy, 2018). Antipsychotic drugs, particularly atypical (or second-generation antipsychotics [SGAs]) are first-line treatment for psychotic episodes and the symptoms of agitation, delusions, and hallucinations that occur with each of the disorders. Despite their adverse effects, first-generation antipsychotics (FGAs) are used as treatment as well. Oral formulations are preferred, but intramuscular (IM) may be used during emergencies (Merck Manual, 2018).
FGAs work by antagonizing dopamine D2 receptors and some of the most common include chlorpromazine (Thorazine), haloperidol (Haldol), fluphenazine (Prolixin), loxapine (Loxitane), molindone (Moban), perphenazine (Trilafon), thioridazine (Mellaril), thiothixene (Navane), and thrifluoperazine (Stelazine). FGAs pose the highest risk for extrapyramidal symptoms (EPSs) among all antipsychotic medications. EPSs are drug-induced movement disorders that are one of the most common adverse effects of centrally acting, dopamine-receptor blocking medications. EPSs are often debilitating and interfere with communication, socialization, motor skills, and activities of daily living. These symptoms can include acute dystonia (spasm 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; D'Souza & Hooten, 2019). Anticholinergic drugs can be used to lessen EPSs. This would include benztropine (Cogentin) and biperiden (Akineton) (Stephen & Lui, 2019). Other less common but potential side effects of FGAs can include orthostasis, QT prolongation, weight gain, seizures, hyperlipidemia, and glucose abnormalities (D'Souza & Hooten, 2019). Refer to Table 2 for a detailed overview of dosing and special conditions of several types of FGAs
Common Types of FGAs
PO: 25 to 2000 mg/day
IM: 25 to 200 mg IM/day
IM injection typically administered to the upper outer quadrant of gluteal. Requires a lower dose with IM than oral (significant oral first-pass metabolism). Use with caution in patients with hepatic or renal impairment.
PO: 5 to 100 mg/day
IM: 2 to 20 mg/day
(2 to 5 mg IM every 4-8 hours)
Contraindicated in patients with severe toxic central nervous system depression or patients who are comatose. Hypersensitivity to this drug can include anaphylactic reaction and angioedema.
PO: 2.5 to 40 mg/day
IM: 10 mg/day
IM dose should be 33-50% of the oral dose. Use is contraindicated with hepatic impairment. Use with caution in renal impairment.
Loxapine (Adasuve) inhaler
PO: 20 to 250 mg/day)
Aerosol Powder Inhalation: 10 mg/day
Loxapine (Adasuve) inhaler is used to treat agitation and requires participation in the REMS program due to the risk for bronchospasm.
PO: 150 to 800 mg/day
Risk for dose-related QTc prolongation. Baseline ECG and serum potassium levels are recommended. Use should be reserved for failure to other antipsychotic drugs. Use with caution in hepatic impairment.
PO: 6 to 60 mg/day
Smoking may interfere with CYP1A2 induction, impairing the metabolism of the drug.
PO: 4 to 50 mg PO/day
Smoking may interfere with CYP1A2, impairing the metabolism of the drug. Contraindicated in hepatic disease.
SGAs include medications such as quetiapine (Seroquel), asenapine (Saphris), aripiprazole (Abilify), brexpiprazole (Rexulti), paliperidone (Invega), risperidone (Risperdal), olanzapine (Zyprexa), ziprasidone (Geodon), cariprazine (Vraylar), lurasidone (Latuda), and clozapine (Clozaril). SGAs work 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. Clozapine (Clozaril) also functions differently as it antagonizes alpha-adrenergic and cholinergic muscarinic receptors. Some of the most common SGAs are outlined in Table 3. EPSs occur less frequently with SGAs than with FGAs; however, EPS risk increases with dose escalation. As a class, SGAs pose a risk for metabolic side effects, such as weight gain, hyperlipidemia, seizures, and diabetes mellitus, which can thereby contribute to the increased risk of cardiovascular mortality in schizophrenia patients. Less commonly, SGAs can cause orthostasis and QTc prolongation (D'Souza & Hooten, 2019). According to the 2015 American Geriatric Society Beers Criteria (BC), antipsychotic drugs should be avoided as a first-line treatment for delirium in older patients unless they are a threat to self or others due to increased risk of stroke and mortality in the elderly with dementia and olanzapine (Zyprexa) syncope (Terrery, 2016).
Common Types of SGAs
PO (IR): 50 to 800 mg/day
PO (ER): 50 to 300 mg/day
IR forms are only marginally affected by food, whereas ER forms are significantly affected if consumed with high-fat meals; it is recommended to take ER tablets without food or with a snack less than 300 calories.
PO: 40 to 160 mg/day
Must be administered with food greater than or equal to 350 calories.
PO: 5 to 20 mg/day
IM: 10 mg/2mL (1 mL to 4 mL/day)
IM used primarily for agitation with the usual dose of 2.5 – 1.0 mg IM (maximum dose is 30 mg/day). Smokers may require a 30% greater daily dose than nonsmokers due to CYP1A2 induction. Females may need lower doses. IM often requires dose reduction by 40% of oral dose due to first-pass metabolism.
PO: 2 to 8 mg/day
Dose adjustment required in patients with CrCl less than 30mL/min or severe hepatic impairment.
PO: 1.5 to 6 mg/day
Use is not recommended with severe hepatic impairment or in renal impairment with CrCl less than 30mL/min.
PO: 12.5 to 900 mg/day
Reserved for treatment-resistant schizophrenia; REMS program due to risk for life-threatening agranulocytosis. Requires monitoring of ANC at baseline and frequent intervals (usually weekly or biweekly); increased risk for orthostatic hypotension and seizures.
PO: 80-160 mg/day
Used for the acute treatment of agitation in schizophrenia. Increased risk of bone fractures with long-term use.
FGAs and SGAs are available in short-acting/IR and ER oral (PO) formulations, as well as short-acting intramuscular (IM) and long-acting injectable (LAI) agents. LAI medications are a practical option for patients who are noncompliant with oral medication therapy. However, clinicians are advised to first determine the etiology of the patient's noncompliance with oral treatment before changing to LAI. If nonadherence is related to undesirable adverse effects of oral treatment, then the patient should first be changed to an alternative oral medication before transitioning to LAI (APA, 2019). When starting antipsychotic medications, clinicians are advised to start at the lowest dose possible and gradually increase the medication dose, as recommended by the individual drug's prescribing guidelines. Agitation and hallucinations typically resolve first (within days), but delusions may take weeks to resolve, and full effects are usually seen by six weeks (NIMH, 2016).
According to the APA (2019) practice guidelines for the treatment of patients with schizophrenia, which are currently available online as a 2019 draft version (final revisions are expected to be published in the summer of 2020), 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 not available due to limitations in clinical trial designs and lack of direct drug-to-drug comparisons. Currently, “there is no definitive evidence that one antipsychotic will have consistently superior efficacy compared with another, with the possible exception of clozapine (Clozaril)” (APA, 2019, p. 52). 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, which is a decline in the white blood cell level, namely the absolute neutrophil count (ANC). Clozapine (Clozaril) is reserved for patients who are resistant to treatment with other antipsychotic drugs, as it is considered the most effective antipsychotic drug for the management of treatment-resistant schizophrenia (Freudenreich & McEvoy, 2018).
The APA guidelines recommend that drug selection is premised on the risks and benefits of the prescribed therapy, individual patient factors such as co-existing medical conditions, the potential for those conditions to be affected by medication side effects, risk for drug interactions, psychosocial support, patient and family preference, as well as the feasibility of compliance with chosen therapy. Before starting antipsychotic therapy, the clinician is advised to obtain a complete and thorough medication history, reviewing current medications, any antipsychotic medications used in the past, and the patient's tolerance for treatment. It is critical to assess for any drug allergies, medication interactions, or contraindications to drug therapy. Clinicians must also assess the potential benefits of treatment as well as the potential harms of untreated illness with regards to the potential for negative fetal or neonatal effects in females of childbearing age. 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 mother-infant bonding. In addition, all psychotropic medications appear to cross the placenta, have been found in amniotic fluid, and in human breast milk (APA, 2019).
Monitoring of Patients on Antipsychotics
While there are several important monitoring domains 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 such as weight gain, hyperlipidemia, and hyperglycemia worsen throughout the duration of therapy. Furthermore, EPSs 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, 2019).
Some antipsychotic medications require strict monitoring as outlined by the FDA Risk Evaluation and Mitigation Strategy (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 (US Food and Drug Administration [FDA], 2019).
As recommended by consensus guidelines put forth by the American Diabetes Association, American Psychiatric Association, and the American Association of Clinical Endocrinologists in 2004, patients on SGAs should undergo the following monitoring parameters at baseline and at follow up visits as specified below.
- Personal and family history of obesity, diabetes, hyperlipidemia, hypertension, or cardiovascular disease (baseline and annually)
- Weight and height, or BMI (baseline, four weeks, eight weeks, 12 weeks, quarterly, and annually)
- Waist circumference (baseline and annually)
- Blood pressure (baseline, 12 weeks, and annually)
- Fasting plasma glucose (baseline, 12 weeks, and annually)
- Fasting lipid profile (baseline, 12 weeks, and annually) (American Diabetes Association et al., 2004; Magellan Health, 2017).
Mood stabilizers decrease manic and hypomanic symptoms that may occur during psychotic episodes or when the schizoaffective disorder is of the bipolar type. While significant evidence does not exist in the use of these medications with psychotic disorders, there is the ongoing support for them as adjunctive therapy to manage the symptoms and potential co-morbidities of psychotic disorders. Mood stabilizers work to level out the manic highs and depressive lows (Mayo Clinic, 2019a). Lithium (Lithobid), a commonly prescribed mood stabilizer that works by altering sodium transport across neurons, is approved for the treatment of psychotic disorders, including schizophrenia. There is moderate concern about safety and tolerability with lithium (Lithobid) use long term as it is considered possibly hazardous in breastfeeding moms (Yatham et al., 2018). Alternatives for mood stabilization include anticonvulsants such as divalproex sodium (Depakote), valproic acid (Depakene), carbamazepine (Tegretol), and lamotrigine (Lamictal) (NIMH, 2016).
Regarding safety and tolerability for long term use, divalproex sodium (Depakote) has moderate safety and minor tolerability concerns, and carbamazepine (Tegretol) has minor safety and moderate tolerability concerns, while lamotrigine (Lamictal) has very limited 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 evaluate for 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
- Excessive thirst
- Frequent urination
- Nausea and vomiting
- Slurred speech
- Fast, slow, irregular, or pounding heartbeat
- Blackouts (loss of consciousness)
- Changes in vision
- Loss of coordination
- Swelling of the eyes, face, lips, tongue, throat, hands, feet, ankles, or lower legs (NIMH, 2016).
Patients who are taking mood stabilizers should have specific monitoring based on the medication prescribed. Those on lithium (Lithobid) should have serum lithium levels evaluated following one week of therapy, following all dose adjustments, in the presence of any concerning side effects, and annually. They should also have their thyroid-stimulating hormone (TSH) checked at baseline, two weeks, six weeks, and then annually. The renal function should be evaluated at baseline, two weeks, and then annually. Patients who are prescribed valproic acid (Depakene) should have serum levels evaluated one week of therapy, following all dose adjustments, in the presence of any concerning side effects, and annually. In addition, they should have their liver function tests (LFTs) checked at baseline, two weeks, and annually, as well as if any symptoms or clinical suspicion for hepatitis develops. A CBC should be evaluated after two weeks, six months, and then annually unless the patient develops any signs of easy bruising or bleeding, which should prompt additional CBC testing. For patients taking carbamazepine (Tegretol), serum drug levels should be monitored at one week, four weeks, annually, and with any dose increases. These patients should have a CBC checked at one week, one month, four months, and annually. Sodium level should be checked at one week and then annually, and LFTs should be checked at two weeks and annually. With oxcarbazepine (Trileptal), patients should have their sodium level checked at baseline and at one month. Patients on lamotrigine (Lamictal) do not require any laboratory monitoring (How & Xiong, 2019).
Some of the psychotic disorders have depressive features and benefit from the use of antidepressants, particularly schizoaffective disorder and postpartum psychosis. Depression may be the underlying mood disorder that leads to psychotic symptoms (Joseph & Siddiqui, 2019). The majority of FDA-approved prescription medications for depression target the three neurotransmitters traditionally associated with depression: serotonin, norepinephrine, and dopamine. These antidepressants usually take at least two to four weeks before they start to take effect. Symptoms such as sleep, appetite, and concentration often improve before a notable change in mood. Due to their side effect profiles, most antidepressants need to be tapered up slowly when starting therapy and tapered down gradually when stopping treatment. If stopped abruptly, some antidepressants pose a risk for withdrawal-like symptoms such as dizziness, headache, flu-like syndrome (tiredness, chills, muscle aches), agitation, irritability, insomnia, nightmares, diarrhea, and nausea. In women of childbearing age, they should be warned 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 in lactating mothers (NIMH, 2016).
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 expanded a few years later to include all young adults, especially those under the age of 25, stating that these individuals may experience an increase in suicidal thoughts or behaviors during the first few weeks of taking an antidepressant 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 for suicide. Further, clinicians are advised to ask patients about suicidal thoughts before prescribing antidepressants to young persons (FDA, 2018). Table 4 provides a list of the points that must be included in the boxed warning.
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 closely observe the patient and to communicate with the prescriber.
A statement regarding whether the particular drug is approved for any pediatric indication(s) and, if so, which one(s).
Selective serotonin reuptake inhibitors (SSRIs) are usually the safest initial choice, cause the least side effects, and are the preferred antidepressant with most psychotic disorder treatments. SSRIs include drugs such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac), fluvoxamine (Luvox CR), paroxetine (Paxil), and sertraline (Zoloft) (Mayo Clinic, 2019b). 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 (Mayo Clinic, 2019a).
Common Side Effects of SSRIs
Possible Side Effects
Nausea, vomiting, diarrhea, headache, dry mouth, drowsiness, insomnia, nervousness, agitation, restlessness, sexual dysfunction, appetite change leading to weight loss or weight gain
Warnings and Monitoring
Risk for withdrawal symptoms if stopped abruptly
(Mayo Clinic, 2019a)
While antidepressants typically do not require routine laboratory monitoring or drug levels, prescribers should remain alert to the potential side effects and adverse effects outlined in Table 5 above. Further, SSRIs are rarely associated with hyponatremia, bleeding, and a decline in bone density. Prescribers should perform a routine evaluation of patients on SSRIs and should consider ordering laboratory testing to evaluate for hyponatremia if patients experience any of the following rare but possible medical complications. Bleeding events in patients on SSRI therapy most commonly present as GI bleeding, although this is rare (Terrery, 2016).
Concerning pharmacological therapy for the treatment of anxiety, benzodiazepines are among some of the most commonly used medications for the immediate and short-term relief of acute symptoms of anxiety. Benzodiazepines work by enhancing the effects of gamma-aminobutyric acid (GABA) in the brain (NIMH, 2016). 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 management of anxiety, such as for minor medical procedures. While benzodiazepines have the advantage of a very fast onset of action and are highly effective in alleviating acute symptoms, they are schedule IV controlled substances according to the DEA. In some states, they are classified as Schedule II due to a high risk of abuse and dependence. 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 benzodiazepine include drowsiness or tiredness, dizziness, nausea, blurred vision, headache, confusion, and nightmares (NIMH, 2016). Most benzodiazepines were previously categorized by the FDA as pregnancy category D or X (positive evidence of risk), and women of childbearing age should be counseled extensively on their individual risk before starting a benzodiazepine (NIMH, 2018). The most recent version of the BC recommends that benzodiazepines be avoided in older patients for insomnia, agitation, or delirium due to fall risk and high rate of physical dependence, especially longer-acting versions (Terrery, 2016).
A study by Torrisi et al. (2017) identified the potential use of Buspirone (Buspar) as a therapeutic medication in the treatment of schizophrenia. Buspirone (Buspar) is approved for the treatment of chronic anxiety, but it is not a benzodiazepine and is not 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 does not work when taken on an as-needed basis. Adverse effects of buspirone (Buspar) include dizziness, headache, nausea, nervousness, lightheadedness, excitement, and trouble sleeping, and was categorized by the FDA as pregnancy category B (no evidence of risk) (NIMH, 2016).
Specific Disorder Treatments
Brief Psychotic Disorder
Psychotherapy for the patient with brief psychotic disorder would include informing the patient and their family or loved ones about their condition and opportunities for treatment with their condition. This condition is disruptive to the daily functioning of the individual’s life as well as those around them. Reintegration into their social milieu is crucial. Management of comorbid disorders and stressors should be part of the nonpharmacologic treatment for brief psychotic disorder as well as 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. Pharmacotherapy for brief psychotic disorder typically includes SGAs. Additional medications are FGAs, anticholinergic drugs to lessen the EPS symptoms, and benzodiazepines to decrease acute agitation or if patients become acutely combative (Dryden-Edwards, 2018; Stephen & Lui, 2019).
Since there is limited insight into this disorder, treatment can be difficult. A consistent and trusting relationship with a healthcare provider is paramount for success. Hospitalization is not typically needed. Treatment includes psychotherapy based on a therapeutic alliance between the patient and provider. The patient’s history with medication compliance should be considered in determining the best antipsychotic medication. Antipsychotics should be started for a trial period of six weeks with a subsequent evaluation of effectiveness. Low doses are recommended on initiation, then titrate up as needed. After six weeks, an alternative drug class can be considered until goals of treatment are achieved. Mood stabilizers such as lithium (Lithobid) valproic acid (Depakene), or carbamazepine (Tegretol) can be added to therapy if a single therapy with antipsychotics is not effective, but compliance may be more difficult with multiple medication therapies. Combination psychotherapy and pharmacotherapy provides the best treatment response (Joseph & Siddiqui, 2019).
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 type. Hospitalization may be needed initially followed by long-term treatment to manage the ongoing symptoms. Psychotherapy can be done individually or in a group. Group therapy may involve the entire family, as this disorder impacts relationships and family dynamics. Both the individual and family need an understanding of the disorder and the treatment plan. The individual should develop a trusting relationship with their healthcare provider during individual therapy. The family should be coached on how to provide reality checks for the patient during periods of psychosis, facilitate appropriate medication management, and develop better social skills for the individual and family. Life skills training focuses on improving communication and socialization with others as well as participation in daily activities. Vocational rehabilitation can help the person with schizoaffective disorder to prepare for employment and then find and keep a job (Mayo Clinic, 2019a). Electroconvulsive therapy (ECT) is a treatment recognized as beneficial to patients with psychosis related to schizoaffective disorder that is unresponsive to traditional pharmacotherapy (Rai et al., 2015).
The only FDA approved antipsychotic for schizoaffective disorder is paliperidone (Invega). Doctors may prescribe other antipsychotic medications to manage the psychotic symptoms. Further options include mood stabilizers that can help level out the manic highs and depressive lows and antidepressants when depression is the underlying mood disorder. (Mayo Clinic, 2019a).
Treatment for schizophrenia is multifactorial and lifelong, It includes pharmacological management in combination with psychosocial support. Hospitalization is often needed, according to the severity of symptoms. 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, social workers, in addition to educational and employment service involvement. CSC is especially helpful in patients with schizophrenia at reducing symptoms, improving quality of life, increasing compliance with medication therapy, and enhancing outcomes (NIMH, 2016). Electroconvulsive therapy (ECT) is a treatment recognized as beneficial to patients with psychosis related to schizophrenia that is unresponsive to pharmacotherapy (Rai et al., 2015).
According to the APA (2019) practice guidelines for the treatment of patients with schizophrenia, SGAs are considered first-line treatment. As previously mentioned, clozapine (Clozaril) is the only medication within the class of SGAs that is not recommended as first-line treatment; it is reserved for patients who are resistant to treatment with other antipsychotic drugs due to safety concerns. Clozapine (Clozaril) is still considered the most effective antipsychotic drug for the management of treatment-resistant schizophrenia (Freudenreich & McEvoy, 2018).
As schizophreniform disorder is a short-term type of schizophrenia, it is treated similarly. The goal of treatment is to stabilize and protect the patient from harm. Hospitalization may be needed, according to the severity of symptoms. People that are likely to cause harm to themselves or others will be treated more aggressively as with all the psychotic disorders. This disorder responds best to both psychotherapy and pharmacotherapy, and both individual and group therapy is indicated. Medications to treat the psychotic symptoms of schizophreniform disorders include SGAs such as risperidone (Risperdal), clozapine (Clozaril), quetiapine (Seroquel), or ziprasidone (Geodon). Once the symptoms improve, and the patient’s behavior and thought patterns have returned to baseline, they should continue treatment for at least 12 months with a gradual tapering of medications and careful monitoring for relapse. Family education to recognize and report relapse is important as well (Cleveland Clinic, 2014).
Timely identification is vital with postpartum psychosis, as the safety of both mother and baby are at risk. In most cases, immediate hospitalization and separation from the infant are required to manage postpartum psychosis. Adjunctive to pharmacotherapy are psychotherapies for the patient suffering from postpartum psychosis. Treatment for postpartum psychosis or other postpartum disorders requires the support of the entire family. Social support, psychoeducation, and psychotherapy are also needed for the family to ensure optimal recovery. The demands and apprehensions regarding the new role can increase anxiety and negative emotions. Individual psychotherapy for the patient can help to smooth the transition into motherhood, reduce depressive symptoms, and improve the adjustment to parenting. Providing reassurance and emotional support can help boost the mother's self-esteem and increase her confidence as a parent. Group psychotherapy may help the patient and family to share their experiences with others. The treatment plan should be created collaboratively with the patient, family, and the healthcare team to determine the best path forward for all involved (Rai et al., 2015).
Mood stabilizers, SGAs, and benzodiazepines may be used with postpartum psychosis. Common treatment includes the mood stabilizer lithium (Lithobid), which is the gold standard in care for postpartum psychosis. Other mood stabilizers include carbamazepine (Tegretol), lamotrigine (Lamictal), and divalproex sodium (Depakote). SGAs including quetiapine (Seroquel) or olanzapine (Zyprexa), and benzodiazepines such as lorazepam (Ativan) or alprazolam (Xanax) are often utilized for postpartum psychosis. Lithium should not be used while breastfeeding and may cause toxicity in the infant. 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 the mother suffering from postpartum psychosis as it leads to insomnia and exhaustion, which can further exacerbate mental health conditions. If lithium (Lithobid) is used, standards of care include proper hydration, serum drug levels, and monitoring of thyroid and renal function during therapy. Furthermore, medication compliance and monitoring for treatment effectiveness remain important throughout the recovery (Monzon et al., 2014; Rai et al., 2015; Raza, 2019). ECT is further considered safe and effective, with few complications, in those with a relapse or exacerbation of postpartum psychosis (Rai et al., 2015).
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