Psychotic Disorders

Joel Johnson MD

Malathi Srinivasan MD

Glen L. Xiong MD

CLINICAL HIGHLIGHTS

Psychosis is a state of disordered thoughts or impairment in reality testing, as manifested by perceptual disturbances (e.g., hallucination) and disorganized speech and behavior.
Secondary psychotic disorders can be caused by general medical conditions (e.g., dementia or delirium with psychosis), side effects from prescribed medications (e.g., prednisone or potent opioid analgesics), severe mood disorders with psychotic features such as depression and bipolar disorder, and illicit substance use.
Positive psychotic symptoms are outward manifestations of the thought disorder: hallucinations, delusions, and bizarre or disorganized behaviors or speech. Negative psychotic symptoms include affective flattening (decreased expressed emotions), alogia (poverty of thoughts), attention deficits, anhedonia, amotivation, and social withdrawal.
The American Psychiatric Association recommends indefinite antipsychotic medication treatment against recurring psychosis in patients with primary psychotic disorders, if two or more episodes occur within 5 years.
Treatment of chronic psychotic disorders, such as schizophrenia, begins with the selection of an appropriate second-generation antipsychotic (SGA) medication and referral for psychosocial services.
Patients who have schizophrenia are at an increased risk for developing metabolic abnormalities. The addition of any SGA carries an additional risk for weight gain, dyslipidemia, and glucose dysregulation. In addition to obtaining the weight and waist circumference at each visit for all patients who are on an SGA, a fasting glucose must be checked before the SGA is started, at week 12 after it was started, and annually thereafter. A fasting lipid panel should also be monitored before the SGA is started, 12 weeks into treatment, and every 3 to 5 years thereafter.

Clinical Significance

The lifetime prevalence of psychotic disorders in U.S. residents is about 3%. In a study of over one thousand urban and academic centered primary care patients, roughly 20% reported some type of psychotic symptom, most commonly auditory hallucinations. Those who have psychotic symptoms are much more likely to experience comorbid depression, anxiety, suicidal thinking and alcohol abuse (1).

The ability to accurately diagnose and effectively treat psychotic disorders has become increasingly relevant for primary care providers for several reasons. First, patients with psychotic symptoms, which complicate general medical conditions (e.g., delusions associated with systemic lupus erythematosus), often present in primary care settings. Second, antipsychotic medications used to treat psychosis have significant potential metabolic side effects (i.e., obesity, hyperglycemia, and hyperlipidemia). As a result, more and more patients who chronically take antipsychotic medications and have been traditionally cared for in mental health programs require primary medical care (2). Third, life-prolonging measures for various medical conditions like Parkinson disease have outpaced the treatment of their associated psychiatric disturbances. The resulting increase in such secondary psychotic conditions has caused an increase in the use of antipsychotic medications, particularly in the last decade.

Diagnosis

PRIMARY PSYCHOTIC DISORDERS

Primary psychotic disorders are conditions in which psychosis is a cardinal symptom and not directly caused by another disorder. Currently,
there are seven defined disorders: schizophrenia, schizophreniform disorder, schizoaffective disorder, brief psychotic disorder, delusional disorder, shared psychotic disorder, and psychotic disorder not otherwise specified (3). Secondary psychotic disorders are clinical conditions in which psychosis is a complicating symptom of a general medical condition or a medication (e.g., encephalitis or the use of high-dose steroids), substance use disorders (e.g., amphetamine- or cocaine-induced psychosis), or mood disorders (e.g., major depression with psychotic features). Patients with relapsing and remitting psychosis usually have a chronic psychotic disorder, representing a primary psychotic disorder. In these cases, symptoms have a high likelihood of recurrence. Patients with untreated psychotic disorders have associated cognitive dysfunction that results in disability, including the inability to work, poor social functioning, poor hygiene, malnutrition, and early death (4). The seven primary psychotic disorders are discussed below.

Schizophrenia

Schizophrenia is the most common primary psychotic disorder in the United States, affecting about 1% of the population. Its economic impact is comparable with that of mood and anxiety disorders, although each of the other two conditions is about 10 times more prevalent than schizophrenia (5). Mortality in those with schizophrenia is about three times that of the general population. About a third of deaths are due to suicide, while a smaller but significant percentage of the deaths are related to violent acts. Approximately 30% of those with schizophrenia attempt suicide and about 10% will die by their attempts (6). Many patients with schizophrenia die of complications of poor life-style choices and poor adherence to medical treatments. Half of those who have schizophrenia are obese and have metabolic syndrome, with a resultant increase in cardiac-related mortality (6). Peak symptom onset is late adolescence or early adulthood, although nonspecific symptoms may be present earlier (7).

Schizophrenia has three phases: (1) a nonspecific prodromal phase, which is usually recognized in retrospect and characterized by subtle behavioral changes, social withdrawal, and functional decline; (2) an active phase, in which psychotic symptoms predominate; and (3) a residual phase, which is similar to the prodromal phase but occurs later in the disease process. Active phase symptoms recur in the residual phase. A definitive diagnosis is generally made in the active phase. The diagnostic criteria for schizophrenia are listed in Table 5.1 (8). Patients with schizophrenia may not (and often do not) present with classic hallucinations or delusions. Instead, they may have extremely disordered thoughts or disorganized behaviors. While patients may have various bizarre delusions, paranoid delusions (i.e., of being watched, followed, plotted against, and harmed) are most consistently present. In order to meet the diagnostic criteria for schizophrenia, some continuous sign of disturbance must be present for at least 6 months.

Table 5.1 Diagnostic Criteria for Schizophrenia

1.	Two positive or negative symptoms: Positive symptoms: hallucinations, delusions, disorganized behavior, and disorganized speech Negative symptoms: flat affect, poverty of thought, social withdrawal, and lack of motivation These criteria can be fulfilled with only one symptom in three special cases:
	a.	A delusional construct that cannot occur in the real world
	b.	Two auditory hallucinations, which are in conversation with each other about the patient
	c.	An auditory hallucination, which provides a running commentary on the patient’s thoughts and/or behaviors
2.	Evidence of symptoms for at least 6 months The syndrome usually starts with negative symptoms or progressively worsening positive symptoms.
3.	Not due to a complication of a systemic medical disorder or other psychiatric disorder
4.	Significant decline from previous level of function
Adapted from American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed., text revision. Washington, DC: American Psychiatric Publishing, Inc.; 2004.

Schizophreniform Disorder

Schizophreniform disorder is often thought of as “early schizophrenia” and is not due to another psychiatric or a general medical disorder. If criteria for schizophrenia are met and symptoms are present for less than 6 months but greater than 1 month, then the diagnosis of schizophreniform disorder is indicated. All patients with schizophreniform disorder should be immediately referred to a psychiatrist with concerns of new-onset psychosis.

Brief Psychotic Disorder

A brief psychotic disorder is also referred to as time-limited schizophrenia. If criteria for schizophrenia are met for more than 1 day but less than 1 month, followed by full clinical recovery, the patient may be diagnosed with a brief psychotic disorder. This diagnosis has a fairly good prognosis and is usually coupled with a significant psychosocial stressor.

Schizoaffective Disorder

Simply put, schizoaffective disorder is schizophrenia with a persistent mood disorder. Someone with schizoaffective disorder simultaneously meets the diagnostic criteria for schizophrenia and either bipolar disorder or major depressive disorder. In order to meet the diagnostic criteria for schizoaffective disorder, there must be evidence that psychotic symptoms are present when the mood disturbance is quiescent for at least a 2-week time period. In general, schizoaffective
disorder carries a poor long-term prognosis that is similar to or worse than schizophrenia.

Delusional Disorder

Those who have delusional disorder present with nonbizarre delusions for at least 1 month. Nonbizarre delusions refer to plausible but unlikely events that could happen in real life. For example, a person may believe that his spouse is poisoning his meals for no apparent reason. Those who have one or more nonbizarre delusions should only be diagnosed with delusional disorder when there is related social or occupational dysfunction due solely to the delusion.

Shared Delusional Disorder

Shared delusional disorder (also called “folie á deux”) is rare and occurs when two individuals in close proximity share the delusion. Patients with shared delusional disorder should be screened for recent stressors as well as anxiety, mood, and disorders related to substance abuse.

Psychotic Disorder Not Otherwise Specified

Patients with psychotic disorder not otherwise specified (NOS) have clinically significant symptoms that don’t meet criteria for a specific psychotic disorder. For example, patients may present with isolated auditory hallucinations, postpartum psychosis in the absence of a mood disorder, or transient stress-induced psychosis. Psychosis NOS often serves as a working diagnosis that may be used while investigating the cause of psychotic symptoms. In order to be diagnosed with psychosis NOS, the symptoms should cause clinically significant distress and not be caused by other general medical or psychiatric illness. For example, an isolated, nondistressing visual hallucination on waking (hypnopompic hallucination) does not merit a psychiatric diagnosis.

PATIENT ASSESSMENT

Patients with psychosis may present in a variety of ways, often with distressing hallucinations or paranoid delusions. More frequently, patients are brought in by family members with a complaint of bizarre behavior, insomnia, or lack of concern for hygiene and grooming. Family members may be concerned over other decline in basic activities of daily living (ADLs) or the patient’s failure to keep up with routine social duties. Many patients have little insight into their psychosis although they will often concede that their thinking is impaired. The provider should assess how the psychosis has disrupted the patient’s ADLs, interpersonal relationships, school or work performance, and financial well-being. Asking about educational, occupational, and social background will help place the current level of functioning in perspective. Table 5.2 summarizes the evaluation
process of patients who present with psychotic symptoms using the PSΨCHOSIS mnemonic.

Table 5.2 Assessment of Patients with Psychotic Symptoms: PSYCHOSIS Mnemonic

Psychotropis: Ask the patient about past use of antipsychotic and other psychiatric medications; including questions related to efficacy and side effects.

Safety first: When in the room, keep in mind the patient’s frame of reference and state of mind. The patient may be scared, paranoid, uncomfortable, potentially violent, angry, or confused. Be prepared to modify your approach as circumstances change in the interview. If the patient seems angry, have a staff member in the room with you, keep the door open, and notify security.

Ψ symptoms: Let the patient know that many other people experience these symptoms and that treatment is available. The clinician can use the following statements to reassure and calm the patient who presents with psychosis: “Many patients in my practice have experienced [symptom]. Is that something that you have experienced as well?” or “I know this is new and may be scary, but I want you to know we can work as a team to make things better.”

Caring: Elicit symptoms with a caring, neutral stance, in which you neither challenge nor collude with the patient’s symptoms. Often, empathizing with the distress around a symptom without validating the symptom is comforting. For example, you might say, “It must be very frightening to believe the FBI is watching you. Let me know what I can do to make you feel less anxious about this.”

Home: Inquire about the living and financial situation, as patients who have a psychotic disorder often struggle with securing safe and stable housing and consistent meals.

Other conditions: Evaluate and treat coexisting general medical, psychiatric, and substance misuse conditions. As with any other medical conditions, assess symptom onset, duration, fluctuation, exacerbating/relieving factors, and associated symptoms.

Suicide: Assess for suicidal and other critical symptoms, such as homicidal thoughts or extreme neglect and inability to care for self. Distinguish between thoughts of death (self or others), plans to harm (self or others), and the degree of development of the plans. All patients who express thoughts of suicide or homicide should be asked about access to a firearm. When indicated, consult with a mental health crisis intervention team or local emergency department.

Impairment: How impaired is the patient because of these symptoms? How have they impacted the patient’s family, work, education and relationships?

Substance misuse: People with schizophrenia frequently have comorbid substance abuse or dependence. Moreover, the use of excessive alcohol or illicit drugs dramatically worsens the prognosis of schizophrenia. All patients who have a psychotic disorder should be regularly monitored for a substance misuse disorder.

Differential Diagnosis

Psychosis is a symptom that, like chest pain, has a broad differential diagnosis. Not all psychotic symptoms are due to schizophrenia! In fact, psychotic symptoms may be due to primary psychosis (e.g., schizophrenia), general medical, other psychiatric, or substance-induced conditions. Figure 5.1 illustrates an approach to patients presenting with psychotic symptoms. In general, acute, isolated psychotic symptoms are due to substance use, medication side effects, or a general medical condition since primary psychosis and secondary psychosis due to another psychiatric disorder (e.g., bipolar disorder) tend to have a more subacute to chronic course with progressive worsening. When forming a differential diagnosis, we recommend taking the following stepwise approach (9).

Figure 5.1 Diagnostic algorithm for psychosis. (Adapted with permission from the American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed., text revision. Washington, DC: American Psychiatric Publishing, Inc.; 2004.)

STEP 1: ELICIT SYMPTOMS

The provider should elicit the course and fluctuation of symptoms and the impact on social functioning. Positive psychotic symptoms are outward manifestations of the psychosis: hallucinations, delusions, and bizarre or disorganized behaviors or speech. Negative psychotic symptoms are the “fall from function” symptoms: flat affect, poverty of thought, social withdrawal, apathy, and lack of motivation. Table 5.3 defines common psychotic symptoms. For acutely psychotic patients, the best way to elicit symptoms is to take a caring, neutral stance in which the provider neither challenges nor colludes with the patient’s
symptoms. Often, empathizing with the level of distress can be done without challenging or confirming the symptoms. For example, one might say, “It must be frightening and frustrating to believe your coworkers are monitoring your every move while at work and home.” Collateral information sources should be obtained to supplement the subjective history whenever possible.

Table 5.3 Definition of Psychotic Symptoms

POSITIVE SYMPTOMS	WHAT ARE THEY?	OFTEN CONFUSED WITH…
Hallucinations	Sensory perception in the absence of sensory stimuli. May occur with any of the senses (visual, auditory, olfactory, skin sensations, etc.)	Perceptual distortions or illusions: sensory misperception in the presence of stimuli (e.g., mistakenly identifying a chair as a person) “Mystical experiences,” often part of a spiritual belief system May be due to medical disorders (temporal seizures, migraine auras, uremia, hepatic encephalopathy, etc.)
Delusions	Fixed belief that is at odds with reality (delusions of persecution, grandeur, parasites, etc.)	Beliefs due to environmental, social, cultural, or spiritual/religious background (e.g., belief in God’s influence over health or destiny, transfer of the soul with blood transfusions, breaking a mirror brings bad luck, etc.)
Bizarre delusions	Not physically possible (e.g., people walking through walls or traveling back in time)	Nonbizarre delusions are possible, but untrue—for instance, a patient feeling that “a celebrity is in love with me”
Thought disorder	Disorders of thought process or how one thinks. Patients may have difficulty with logical construction of thoughts (tangential, word salad, flight of ideas, loosening of associations, neologisms, etc.) or expression of their thoughts in unintelligible ways	Delirium, dementia, aphasia, mania
Bizarre behaviors	Inability to dress, act, or interact in socially appropriate ways. Behaviors may be crude (cursing, solicitous), offensive, violent, or erratic Dress in poorly fitting clothing, wear makeup smeared over the face or buttons mismatched and zippers undone Urinate or defecate in unusual places, even if a bathroom is nearby	Social trends (intergenerational conflicts), unusual fashions, fads, or social groups with nonconformist behaviors

STEP 2: EVALUATE FOR SYSTEMIC MEDICAL CONDITIONS

Psychosis may be caused by illicit or prescribed drugs, infections, vasculitis, autoimmune disorders (e.g., systemic lupus erythematosus), poisoning (e.g., heavy metals), stroke, or dementia. Table 5.4 reviews general medical conditions associated with psychosis and the corresponding work-up. Clinical suspicion should guide diagnostic testing to avoid unnecessary false-positives, inconvenience, and cost. Medical conditions with systemic manifestation (e.g., delirium) often cause acute mental status changes, which often present with acute psychotic symptoms.
Patients with delirium frequently have impaired levels of consciousness, such as disorientation and impaired ability to sustain attention. Dementia should be considered as a causative factor for psychotic symptoms as about 30% of patients with dementia have comorbid psychosis. Table 5.5 helps to distinguish between delirium, dementia, and primary psychosis.

Table 5.4 General Medical Causes of Psychosis

CONDITIONS	PRESENTATION	ASSESSMENT	COMMENTS
Neurologic disorders (chronic) (seizure disorder, Parkinson disease, multiple sclerosis, stroke, Huntington disease, traumatic brain injury)	Acute or progressive development of delusions, hallucinations, disorganized behavior, agitation, and disinhibition Temporal relationship between the neurologic disorder and the psychotic symptoms Psychiatric finding may be the only presentation in cases of isolated neurologic lesions (e.g., stroke or occult multiple sclerosis)	Brain imaging to detect underlying neurologic condition Lumbar puncture for multiple sclerosis	Patients with a primary neurologic condition and psychosis should be given a diagnosis of “psychosis due to a general medical condition,” rather than be diagnosed with schizophrenia Pharmacotherapy may be similar to schizophrenia but antipsychotic-associated EPS may be more likely in this patient population
Neurologic disorders (acute) (central nervous system infection or inflammation, e.g., syphilis, herpes encephalitis, HIV, lupus, vasculitides)	Acute to subacute onset of hallucinations, delusions, agitation, mania, depression, and disorganized behavior Unless the infection or inflammation also involves other organs, minimal systemic findings may be present in the beginning	RPR/VDRL HIV ANA ESR/CRP CBC Lumbar puncture	RPR/VDRL and an HIV test should be considered as part of the work-up of psychosis in those who have risk factors (e.g., use of intravenous drugs, unprotected sex with multiple partners, or a history of sex with prostitutes) Inflammatory markers, ANAs, and more specific antibody tests may also be considered, as clinically indicated
Electrolyte disturbance hypercalcemia, hyponatremia, or uremia)	Acute to progressive course of lethargy, agitation, disorganization, delirium, or hallucinations	Basic chemistry panel with calcium and magnesium	Systemic symptoms are often present In this case, psychosis is probably a component of delirium
Medication-induced psychosis	Acute onset of hallucinations, delusions, disorganization, and cognitive deficits following drug ingestion	Urine drug screen	Opioids, steroids, stimulants, anticholinergics, dopamine agonists, etc. Lithium
ANA, antinuclear antibody; CBC, complete blood count; CRP, C-reactive protein; EPS, extrapyramidal symptoms; ESR, erythrocyte sedimentation rate; HIV, human immunodeficiency virus; RPR, rapid plasma reagin; VDRL, Venereal Disease Research Laboratories.

STEP 3: ADDRESS MEDICATION- OR SUBSTANCE-INDUCED PSYCHOSIS

Medication-induced psychosis is another potential cause of formal thought disorders and perceptual abnormalities. This typically occurs in the elderly population, although it may also occur in patients who have renal or hepatic impairment with reduced drug clearance. Polypharmacy is another potential precipitant of psychotic symptoms as the risk for drug-drug interactions is elevated. Possible culprits include anticholinergics, sedative-hypnotics, opioid analgesics, anticonvulsants, theophylline, digoxin, and some antidepressants. The most important clue in such cases is the clinical history and timing of symptoms in the susceptible patient.

Psychotic symptoms may occur due to substance intoxication and withdrawal. Psychoactive substances range from phencyclidine (PCP), lysergic acid (LSD), cocaine, methamphetamines, alcohol, and marijuana. Patients with a history of alcoholism may have a related thiamine deficiency and develop Korsakoff psychosis with resultant confabulation, deficits in memory, and diminished ability to perform ADLs. Patients may also develop transient psychotic symptoms in the setting of alcohol withdrawal or delirium tremens. Cocaine and methamphetamine intoxication-related psychosis is very similar to that of the paranoid subtype of schizophrenia. Most substance-induced psychoses resolve over a brief period of time (usually 3 hours to 3 days of detoxification) and therefore would not require prolonged treatment other than counseling about cessation from the offending substance. However, some substances like ecstasy or methylenedioxymethamphetamine (MDMA) may cause persistent psychotic symptoms. The causal association may be difficult to establish and usually requires at least a 3- to 4-week period of sobriety to solidify a diagnosis and treatment plan. Many patients with chronic psychosis are also at high risk for comorbid substance use and should be monitored accordingly.

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