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4. Drug-Induced Psychosis
Keywords
Drug-induced psychosisDiagnosisTreatmentUrine drug testingAlcoholSedativeCannabisStimulantsMethamphetamineLSDHallucinogensPCPKetamineMedication-induced psychosisToxinsEssential Concepts
Some drugs of abuse cause psychosis during intoxication (or during withdrawal in the case of alcohol or sedative-hypnotics). Prolonged psychosis is typical for phenylcyclohexyl piperidine (PCP) and methamphetamines.
History of drug ingestion supported by urine drug testing and resolution of symptoms in a manner characteristic for the drug suggests a drug-induced psychosis.
A diagnosis of drug-induced psychosis is prognostically ominous. In up to 50% of cases of cannabis-induced psychosis, patients are later diagnosed with a serious mental disorder like schizophrenia.
Chronic alcoholism can cause chronic psychosis in the form of alcoholic hallucinosis and delusional jealousy (Othello syndrome).
Synthetic cannabinoids and high-potency cannabis have increased the risk for psychosis during intoxication and also for triggering schizophrenia. Cannabis is considered a component cause for schizophrenia in vulnerable people.
Stimulants and hallucinogens predictably cause a usually short-lived, drug-induced psychosis (methamphetamine psychosis can last weeks).
PCP can cause a severe, agitated psychosis lasting many days.
Therapeutic benefits from hallucinogens (e.g., reducing existential anxiety in cancer) and ketamine (e.g., rapid reversal of acute suicidality) are actively studied.
Many medical medications are associated with psychosis as a rare side effect. Glucocorticoids are the most common culprit.
“Drugs are a bet with your mind.” [1]
–Jim Morrison, The Doors, 1943–1971
Many drugs can cause psychosis (delusions and/or hallucinations) in a clear sensorium (i.e., in the absence of a delirium). This is true not only for legal drugs (e.g., alcohol, cannabis) or illegal drugs but also for prescribed medications (e.g., steroids, digoxin), herbal medications, and over-the-counter medications. In this chapter, I discuss patients who present to the emergency department (ED) with drug-induced psychosis (or substance-induced psychotic disorder, in DSM-5 and ICD-11 terminology), including psychosis from medical medications. Drug-induced psychosis is diagnosed in cases where the psychosis is believed to be the direct (physiological) result of the substance, either during intoxication or withdrawal. The assumption for a case of drug-induced psychosis is that psychosis resolves once the responsible drug is removed. For a discussion of comorbid drug use in schizophrenia, see the chapter on Dual Diagnosis (Chap. 26). Several psychoactive drugs are being re-examined for therapeutic use (e.g., 3,4-methylenedioxy-methamphetamine (MDMA) [2] or ketamine [3]) which may result in an increase in cases of psychosis from those drugs.
Diagnosis of Drug-Induced Psychosis
Drug-induced psychosis
During intoxication | During withdrawal | Prolonged | |
|---|---|---|---|
Alcohol | Yes | Yes | Yes |
Sedatives | Yes | Yes | Yes |
Cannabis | Yes | No | With high-potency products |
Stimulants | Yes | No | Yes (methamphetamine) |
Hallucinogens | Yes | No | Not usually |
PCP | Yes | No | Yes |
Opiates | Not usually | Not usually | Not usually |
The diagnosis of drug-induced psychosis is complex and often not straightforward. Clinicians must synthesize a history of drugs use, symptoms, and results of urine drug testing. Knowledge of local drug use patterns are an important clue to a drug intoxication. Chewing the herbal stimulant khat, for example, common in East Africa and associated with psychosis [7], would be an unusual cause of psychosis in a local New England college student where you would rather expect the use of prescription stimulants. Designer drugs, readily available over the internet, have made it difficult to always pinpoint the cause of a drug-induced psychosis [8].
Tip
All drug use is local. Knowing the patterns of use in your community helps with the correct diagnosis and which tests to order. Is your patient from an immigrant community? What drugs are currently common in your high school? Is your patient from a subpopulation (e.g., patient with HIV)?
Ideally, a 4-week period of abstinence is necessary to judge if psychosis resolves in a time consistent with the drug. Unfortunately, the necessary abstinence period is frequently not achieved, and you are left wondering how much psychosis is fueled by intermittent, low-grade drug use.
Patients who receive a diagnosis of substance-induced psychosis have an ominous prognosis with regard to eventually developing a serious mental disorder. In one population-based study, one third of patients given a diagnosis of substance-induced psychosis were eventually diagnosed with bipolar disorder or schizophrenia [9]. The highest conversion rate (about 50%) was seen in patient initially diagnosed with cannabis-induced psychosis. I hesitate to diagnose schizophrenia in an antisocial patient with indiscriminate and heavy drug use (“polysubstance use”), particularly if there are no negative symptoms. Experiencing visual hallucinations may tip the scales toward a drug-induced psychosis, particularly if there is drug addiction and substance use in parents [10]. Patients with good premorbid adjustment, a shorter duration of untreated psychosis, better insight into their psychosis, and less severe psychosis have a good prognosis for recovery from a substance-induced psychosis [11]. Note that these predictors of recovery are identical to good prognosis factors in schizophrenia.
Psychopathology
Unfortunately, the cross-sectional psychiatric symptom picture will not help you determine if a mental state is caused by “functional” psychosis like schizophrenia or if it is drug-induced. In fact, many drugs (e.g., amphetamines) can cause a model psychosis that has helped the field understand the pathophysiology of schizophrenia. Do not rely on Schneiderian symptoms or symptoms thought to be typical for “organicity” (e.g., visual hallucinations) alone to determine if a functional or an organic presentation, respectively, is more likely. Harris and Batki [12] carefully characterized 19 patients with stimulant-induced psychosis; for example 95% had bizarre delusions, 64% had Schneiderian first-rank symptoms, and 26% had substantial negative symptoms.
Key Point
There is no one psychiatric symptom or symptom constellation that is pathognomonic for a drug-induced psychosis.
History of Drug Use
A history of drug use might be unavailable or incomplete. Patients themselves might not know what they ingested or whether they were taken adulterated drugs (e.g., cannabis with PCP). Therefore, urine drug testing is mandatory even in cases in which a specific drug or no drug use is reported.
Tip
The drug subculture has its own lingo. Do not play it cool; ask if you do not know. I always ask what patients mean if they use a drug name, as those are not tightly regulated and patients might use the names differently from you. Names for illicit drugs that you grew up with might also no longer be in use.
Urine Drug Testing
Urine for drug testing should be obtained routinely in psychotic patients who present to the ED. This rule applies to new-onset psychosis but also to patients with established schizophrenia, as comorbid drug use is so common (but not recognized). However, there are limitations to what drug testing can accomplish: you can only detect what you test for. Most urine drug screens (UDS) contain the standard “National Institute on Drug Abuse (NIDA) 5,” cocaine, amphetamines, cannabis, opiates, and PCP, supplemented by benzodiazepines and barbiturates. Note that drugs that interest us in the context of psychosis but are not tested for include LSD, hallucinogens, and the so-called club drugs and synthetic designer drugs. The interpretation of drug testing results is also not straightforward. If a drug test is negative, the timing between ingestion and testing might simply have been too long, and urine drug level fell below the detection limit of the assay. Even if a drug test is positive (and the patient took the detected substance), this does not establish that the drug is in fact responsible for the mental state. Lastly, false-positive drug tests can lead clinicians down the wrong diagnostic path; review the medication list with regard to the possibility of a false-positive drug test. Unfortunately, for immunoassay-based urine drug tests commonly used in the ED setting, any official list of medications known to show cross-reactivity with drugs of misuse is going to be incomplete [13]. Indiscriminate urine drug screening without clinical suspicion (i.e., a situation of low prior probability) is unhelpful and only increases the changes for false-positive test results. A false-positive drug test will unfairly put a patient in the basically impossible position to prove his or her innocence.
Except for serum alcohol level, serum drug testing is rarely useful in the ED unless results are immediately available. Serum cocaine levels can be useful because positive results indicate recent (within a few hours) use. Other tests, such as benzodiazepine levels, might still be useful for diagnostic purposes later on, and you might consider saving a tube of blood.
Treatment of Drug-Induced Psychosis
Deciding how to best treat a self-limited drug-induced psychosis is difficult, as antipsychotic poses some risk (e.g., causing acute dystonic reactions if patients have used cocaine [14]). Consider using benzodiazepines alone as your initial treatment if you think psychosis is drug-induced and mild, and you expect quick improvement (e.g., uncomplicated cocaine intoxication); but do not hesitate to use antipsychotics if benzodiazepine alone prove insufficient. Obviously, you recommend substance use treatment and cessation of substance use.
Specific Substances of Misuse
Alcohol and Sedatives
Several psychotic disorders can occur in patients with alcohol use disorders. Alcohol (and sedatives including hypnotics and anxiolytics) can cause psychosis during intoxication (rare outside a delirium), during withdrawal, or during delirium tremens. In patients with chronic alcoholism, chronic hallucinosis [15] and paranoia to the point of delusional jealousy [16] can develop. Patients with severe alcohol use disorder are at risk for other medical complications which could cause psychosis (e.g., thiamine deficiency [17]).
Clinical Vignette
Maurice, now in his forties, who had been a heavy drinking for two decades, was admitted to a psychiatric inpatient unit after detoxification because of persecutory delusions and persistent auditory hallucinations. He had brought with him tapes he had made to capture the very prominent derogatory voices. No antipsychotics were administered, and his hallucinations resolved completely within a week. Two weeks after admission, we listened to the tapes together. He agreed that there was nothing recorded but maintained: “I know that the voices are on there because I heard them and recorded them.”
This case of a typical alcoholic hallucinosis illustrates that severe alcoholism can result in psychosis. Antipsychotics should be withheld to see if hallucinations resolve during a period of sobriety. It is important to not confuse ongoing psychosis with memories of the deluded state; in this case, the patient was unable to recognize his past experiences as the results of psychosis but he was not actively psychotic. The patient received thiamine to prevent Wernicke-Korsakoff syndrome.
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