Psychosis is a mental health condition characterized by a disconnect from reality. It is marked by hallucinations, delusions, disordered thinking and behavior. Psychosis can be triggered by underlying mental illnesses like schizophrenia and bipolar disorder. However, certain medications are also known to cause drug-induced psychosis in some people. In this article, we will discuss what medications can cause psychotic symptoms, the mechanisms by which they trigger psychosis, risk factors and warning signs of medication-induced psychosis.
Medications that may cause psychosis
Several types of prescription drugs have been associated with drug-induced psychosis. The major drug classes linked to psychotic symptoms include:
Stimulants
Stimulants are drugs that increase alertness, energy and elevate blood pressure, heart rate and respiration. They have an activating effect on the central nervous system. Examples include:
– Amphetamines like Adderall, Dexedrine used for ADHD
– Methylphenidate drugs like Ritalin and Concerta for ADHD
– Cocaine
– Methamphetamine
In high doses or with long-term use, stimulants can trigger psychosis featuring paranoia, hallucinations and delusions. Chronic abuse has also been linked to stimulant-induced psychotic disorder which persists even after stopping the drug.
Dopamine agonists
Dopamine is a neurotransmitter associated with motivation, pleasure, memory, attention and mood regulation. Dopamine agonists are drugs that mimic dopamine activity in the brain. They are used to treat Parkinson’s disease, restless leg syndrome and prolactinomas. Examples include:
– Pramipexole (Mirapex)
– Ropinirole (Requip)
– Rotigotine (Neupro)
– Bromocriptine (Parlodel)
– Pergolide
Dopamine agonists can cause psychosis in some individuals, likely due to overstimulation of dopamine receptors in the brain.
Cholinergic medications
These drugs enhance the action of acetylcholine in the nervous system. They are used for myasthenia gravis, Alzheimer’s disease, glaucoma and intestinal issues. Examples are:
– Donepezil (Aricept)
– Rivastigmine (Exelon)
– Galantamine (Razadyne)
– Pyridostigmine (Mestinon)
Psychotic symptoms like hallucinations and delusions have been reported with anticholinergic drugs, especially in older people.
Glucocorticoids
Corticosteroids like prednisone, dexamethasone and hydrocortisone are used to treat inflammatory disorders like asthma, arthritis and inflammatory bowel disease. Long-term oral steroid use and abrupt withdrawal can trigger psychosis in some people.
Immunosuppressants
Drugs that suppress the immune system like tacrolimus and cyclosporine used after organ transplants can also cause psychotic episodes, likely by impacting brain chemicals.
Antidepressants
While uncommonly, certain antidepressants have been linked to psychotic symptoms:
– Tricyclic antidepressants like imipramine and amitriptyline
– Selective serotonin reuptake inhibitors (SSRIs) like fluoxetine and paroxetine
– Serotonin-norepinephrine reuptake inhibitors (SNRIs) like venlafaxine and duloxetine
Mood stabilizers
– Lithium – may trigger psychosis during toxicity
– Anticonvulsants like valproate have been linked to psychosis in some bipolar patients
Opioid pain medications
– Morphine
– Oxycodone
– Tramadol
– Fentanyl
– Methadone
Opioids can cause psychosis including hallucinations and paranoia. This may be more common with high doses or in physically dependent individuals.
Antihistamines
First generation antihistamines like diphenhydramine are anticholinergic medications that can cause confusion, agitation and hallucinations in some people.
Other medications
– Anti-malarial drugs like chloroquine and mefloquine
– Some antibiotics like penicillin and ciprofloxacin
– Proton pump inhibitors like omeprazole in high doses
– Anti-vertigo drugs like meclizine
– Muscle relaxants like baclofen and cyclobenzaprine
– Anti-emetic ondansetron
So in summary, a wide range of prescription medications across drug classes have been associated with drug-induced psychotic reactions. The common thread appears to be alteration of chemical messaging in the brain.
Mechanisms of medication-induced psychosis
The exact mechanisms by which different drugs trigger psychosis are not fully understood. However, proposed modes of action include:
Dopamine hypothesis
Excess dopamine activity, especially in the mesolimbic pathway of the brain, is linked to development of psychosis. Many psychotogenic drugs directly or indirectly increase dopamine signaling which may precipitate psychotic symptoms. Examples are stimulants, dopamine agonists and drugs that cause dopamine hypersensitivity with chronic use.
Serotonin hypothesis
Alterations in serotonin pathways, specifically excess 5-HT2A receptor stimulation, may contribute to hallucinations and delusions. Drugs like LSD and psilocybin act as 5-HT2A agonists. Some antidepressants also impact serotonin signaling.
Glutamate hypothesis
Glutamate is an excitatory neurotransmitter in the brain. Drugs that impact the NMDA receptors involved in glutamate transmission like ketamine and PCP can trigger psychosis. Loss of parvalbumin-positive GABAergic interneurons that regulate glutamate may play a role.
GABA hypothesis
Reduced GABA, an inhibitory neurotransmitter, is linked to development of psychosis. Some drugs may cause a relative deficiency in GABA allowing excess excitation. For example, chronic use of benzodiazepines can downregulate GABA receptors.
Cholinergic hypothesis
Anticholinergic medications block acetylcholine activity which may disinhibit dopamine pathways. Excess acetylcholine may also contribute to psychosis.
Inflammation hypothesis
Neuroinflammation may play a role in schizophrenia. Drugs like corticosteroids that suppress inflammation may unmask psychosis upon withdrawal.
Stress and social defeat hypothesis
Stress and trauma can trigger underlying psychosis. Drugs like stimulants may cause psychosis partially through activating the body’s stress response.
So in summary, multiple neurotransmitter systems and neurological pathways appear involved in medication-related psychosis, but dopamine signaling is probably the final common pathway. Genetic variability likely influences individual susceptibility.
Risk factors
While any person can potentially develop drug-induced psychosis, certain factors can increase risk:
– Personal or family history of psychotic disorders like schizophrenia – reflects underlying vulnerability
– Elderly age – due to drug sensitivity, polypharmacy, neurodegeneration
– Adolescents and young adults – maturational changes in dopamine systems
– Substance abuse especially stimulants like methamphetamine
– High doses of medications that affect the CNS
– Abrupt changes in dosage – either increasing or decreasing
– History of traumatic brain injury or stroke
– Dementia – increased sensitivity to psychotogenic medications
– Concurrent use of other drugs that alter neurochemistry like antidepressants, anticholinergics
– Lack of sleep, stress
– Medical conditions that affect the CNS like brain tumors, infections, autoimmune disorders
Warning signs and symptoms
The typical symptoms of drug-induced psychosis include:
– Hallucinations – most often auditory like hearing voices, but can involve any of the senses
– Delusions – fixed, false beliefs like paranoia about persecution
– Disorganized, incoherent speech and behavior
– Cognitive issues like confusion, memory problems
– Apathy, lack of emotion, flat affect
– Agitation, irritability, hostility
– Manic symptoms like rapid speech, hyperactivity, recklessness in some cases
– Social withdrawal and isolation
The following can indicate emerging psychosis related to medication use:
– New onset of nervousness, suspiciousness
– Mood changes like depression or euphoria
– Sleep disturbances like insomnia
– Vivid or disturbing dreams
– Detachment from reality
– Isolating from family/friends
– Difficulty communicating
– Decreased attention span
– Issues at school or work
– Lack of motivation, energy
– Reckless behavior
– Rapid shifts in emotions
In older individuals, psychosis may manifest as worsening confusion or memory problems. Seeking medical help at the earliest signs is important to prevent progression of symptoms.
Diagnosis
Diagnosing medication-induced psychosis involves:
– Medical history – onset and course of symptoms, prescription and illicit drug use, preexisting psychiatric disorders
– Mental status exam – observing speech, behavior, appearance, mood and thought patterns
– Physical exam and tests to identify medical causes like infections, electrolyte abnormalities, brain disorders
– Assessing symptoms against diagnostic criteria for substance/medication-induced psychotic disorder which requires:
– Prominent delusions or hallucinations like hearing voices
– Symptoms arising during or soon after substance intoxication or withdrawal or after medication use
– Symptoms are not better explained by a primary psychotic disorder like schizophrenia
– Considering differential diagnoses like delirium, mood disorders with psychotic features
– Obtaining collateral history from family members
Timing of symptoms in relation to drug use and resolution after discontinuation help confirm causality. Testing blood levels of medications can also clarify if toxicity was a factor. Ultimately a comprehensive evaluation is needed to diagnose medication-induced psychosis.
Treatment
The mainstay of treatment for drug-induced psychosis is identifying and discontinuing the problematic medication under medical supervision. Symptoms typically resolve within days to weeks of stopping the offending drug, although chronic abuse may cause longer-lasting psychosis.
Additional strategies include:
– Switching to an alternative medication if needed for the underlying condition
– Low dose antipsychotics like olanzapine or quetiapine on a short-term basis can help manage acute psychotic symptoms.
– Anti-anxiety medications like benzodiazepines may be used very briefly if symptoms like agitation, insomnia, or catatonia are present.
– Hospitalization is warranted if the person poses a danger to themselves or others.
– Treating associated medical issues like infections, metabolic disturbances, vitamin deficiencies.
– Electroconvulsive therapy in severe refractory cases if psychosis persists despite drug discontinuation.
– Addressing substance abuse if present.
– Psychosocial support and cognitive behavioral therapy can aid functional recovery after psychosis.
Identifying and removing the causative medication combined with 24-hour monitoring during the acute phase is essential. In most cases, drug-induced psychosis resolves fully after stopping the offending agent if there is no underlying psychotic disorder.
Prevention
The following strategies can help prevent drug-induced psychosis:
– Educating patients, families about psychosis risk with certain medications
– Using lowest effective doses of high-risk medications
– Monitoring mental status, especially in first few months after starting treatment
– Screening for personal or family history of mental illness
– Avoiding polypharmacy and drug interactions
– Tapering doses gradually under medical supervision
– Managing stress, improving sleep and nutrition
– Encouraging therapy and social support to cope with life stressors
– Considering lower risk alternatives where possible
– Favoring short-term over long-term treatment with psychotogenic drugs
– Watching for early signs like sleep changes or suspiciousness
– Discussing risks vs benefits before starting medications
Exercising vigilance and closely collaborating with the prescribing doctor can help mitigate the risk of medication-related psychosis.
Conclusion
A number of prescription medications across drug classes have been associated with inducing psychotic symptoms like hallucinations and delusions in some individuals. First generation antipsychotics like haloperidol can also cause psychosis. Stimulants, dopamine agonists, corticosteroids and anticholinergic drugs carry the highest risk. Drug-induced psychosis likely results from the complex effects these agents have on dopamine, serotonin, glutamate, acetylcholine and other neurotransmitters. While difficult to predict who will develop psychosis, risk is increased with overdose, chronic use, personal or family history of mental illness, and conditions affecting the brain. If caught early, medication-induced psychosis generally resolves fully after stopping the problematic drug under medical supervision and initiating temporary antipsychotics if needed. Raising awareness of psychotogenic medications and careful monitoring can help prevent drug-induced psychosis episodes.
