Dozens of medications and substances can trigger a catatonic state, and the list extends well beyond the psychiatric drugs most people would suspect. Catatonia was long assumed to be a feature of schizophrenia, but it is now recognized across mood disorders, medical illnesses, and drug-induced or toxic states. The condition involves a dramatic disruption of movement and behavior, from frozen immobility and mutism to agitated, purposeless activity, and identifying the offending drug is critical because the wrong treatment can make things worse.
Antipsychotics and the Central Paradox
The single most commonly implicated drug class is antipsychotics, which is deeply ironic because these are often the very medications prescribed for the psychiatric conditions that cause catatonia in the first place. Both older (typical) antipsychotics like haloperidol and chlorpromazine and newer (atypical) ones like olanzapine and paliperidone have been reported to trigger catatonic episodes. A case report documented catatonia emerging shortly after a patient started paliperidone, an active metabolite of risperidone, underscoring that even widely used newer antipsychotics carry this risk.1PubMed Central. Catatonia associated with initiating paliperidone treatment The mechanism likely involves excessive blockade of dopamine pathways in the brain, which can tip certain vulnerable individuals into a catatonic state rather than relieving their psychosis.
This creates a genuine clinical dilemma. A person with schizophrenia or bipolar disorder who develops catatonia may need their antipsychotic stopped rather than increased, even though stopping the antipsychotic could worsen the underlying condition. Making the wrong call, like increasing the dose of an antipsychotic that is actually causing the problem, can push a patient toward a life-threatening escalation called malignant catatonia, which involves dangerously high fevers, muscle breakdown, and organ failure.
When Stopping a Drug Triggers Catatonia
It is not just starting a medication that can cause catatonia. Abruptly discontinuing certain drugs is equally dangerous. Benzodiazepine withdrawal is one of the better-documented triggers: in people with mood or psychotic disorders, running out of a benzodiazepine or stopping it suddenly can precipitate a full catatonic episode. One published case involved a 26-year-old man with schizoaffective disorder who ran out of lorazepam and presented with catatonia, delirium, and seizures.2PubMed Central. Benzodiazepine Withdrawal Catatonia, Delirium, and Seizures in a Patient With Schizoaffective Disorder Clonazepam withdrawal has been reported to do the same, and while the exact mechanism is not fully understood, it likely involves a sudden drop in the brain’s inhibitory signaling.3PubMed. Clonazepam withdrawal-induced catatonia
Antipsychotic withdrawal can also produce catatonia. A case series of four patients found that stopping both typical and atypical antipsychotics precipitated catatonic episodes that were potentially life-threatening but reversible with prompt benzodiazepine treatment.4Industrial Psychiatry Journal. Antipsychotic withdrawal-induced catatonia: A four-case series Discontinuation of clozapine specifically appears frequently in the literature as a trigger. The broader lesson is that any medication affecting dopamine or the brain’s inhibitory systems should be tapered carefully rather than stopped cold, especially in patients with a psychiatric history.
Alcohol withdrawal belongs in this category too. A case report described a 28-year-old man with a decade of heavy drinking who developed acute catatonia after about 72 hours of abstinence, presenting with mutism, posturing, waxy flexibility, and mask-like facial expression. Intravenous lorazepam resolved the catatonia completely, but delirium tremens followed within an hour and required its own treatment.5Academic Bulletin of Mental Health. Alcohol Withdrawal Presenting with Catatonia Followed by Delirium Tremens: A Clinical Case Report The case illustrates that catatonia and the more familiar withdrawal syndromes can coexist and need to be managed simultaneously.
Other Prescription Drugs on the List
The range of medications implicated in catatonia is broader than many clinicians expect. A narrative review for hospital physicians listed disulfiram, aspirin, lithium, baclofen, steroids, anticonvulsants, antibiotics, antiretrovirals, bupropion, and chemotherapy agents (particularly tacrolimus) as all having reports linking them to catatonia.6American Journal of Medicine Open. Catatonia: A Narrative Review for Hospitalists Most of these associations rest on case reports rather than large studies, so while the link is real, it is also rare for any single drug outside the antipsychotic class.
A few of these deserve special mention. High-dose corticosteroids like prednisone have caused excited catatonia, a form marked by agitation rather than immobility, even in the absence of any other psychiatric symptoms. One case documented a patient who developed excited catatonia purely from high-dose prednisone, with no psychosis, mania, or depression to explain it.7Academy of Consultation-Liaison Psychiatry. Where, Where, Where? My Fingers Must Be in the Juice: A Rare Look into Steroid-Induced Excited Catatonia in the Absence of Other Psychiatric Symptoms The anti-seizure drug levetiracetam has also been linked to catatonia, with at least one published case describing a 43-year-old woman who developed catatonic symptoms after starting the medication for epilepsy.8PubMed. Catatonia induced by levetiracetam
The challenge with these less-common triggers is that catatonia is often not the first diagnosis that comes to mind. A hospitalized patient on multiple medications who stops speaking and becomes rigid may be evaluated for stroke, severe infection, or worsening of their underlying disease long before anyone considers a drug reaction. Early recognition of drug-induced catatonia was historically held back by the way it was lumped together with catatonia from general medical conditions in research, making it hard to study as a distinct phenomenon.9PubMed. Drug-induced catatonia
Illicit and Recreational Substances
Street drugs and recreational substances add another layer. Cannabis, particularly synthetic cannabinoids (sometimes called “Spice” or “K2”), has been linked to catatonic episodes. A review of published case reports on cannabis-induced catatonia found that the majority of affected patients also developed psychotic symptoms, with most being started on an antipsychotic, which adds complexity because the antipsychotic itself could theoretically contribute to the catatonia.10PubMed Central. Catatonia Induced by First-Time Use of Synthetic Cannabinoids: A Case Report
Synthetic stimulants like mephedrone (a “bath salt” compound) have also been reported to cause delayed-onset catatonia. In one case, a 17-year-old girl with no psychiatric history and no prior drug use developed catatonic symptoms roughly seven days after recreational drug intake, a delay that made the connection to the substance less obvious.11PubMed Central. Delayed drug-induced catatonia in an adolescent girl-clinical implications: a case report The delay matters practically: by the time symptoms appear, both the patient and their family may not connect the episode to the substance use, and emergency physicians may not think to ask about drug exposure from a week earlier.
Why It Looks Like Other Dangerous Conditions
One of the most clinically significant aspects of drug-induced catatonia is that it can look nearly identical to two other life-threatening drug reactions: neuroleptic malignant syndrome (NMS) and serotonin syndrome. All three conditions share features like altered mental status, muscle rigidity, and autonomic instability, and all three can be caused by the same general classes of medication. When a patient has been exposed to both dopamine-blocking drugs and serotonin-affecting drugs, distinguishing between these conditions becomes especially difficult.12PubMed Central. An Unusual Presentation of Serotonin Syndrome and Subsequent Catatonia in a Patient With a Family History of Huntington’s Disease
The distinction is not academic. NMS and catatonia require opposite treatments. NMS demands immediate removal of the offending antipsychotic and supportive care, while some forms of catatonia actually improve with antipsychotic treatment. Lethal catatonia, a syndrome described decades before antipsychotic drugs existed, often begins with extreme psychotic excitement that can progress to fever, exhaustion, and death. NMS, by contrast, typically begins with severe muscle rigidity caused by the drug itself.13PubMed. Clinical differentiation between lethal catatonia and neuroleptic malignant syndrome Because lethal catatonia sometimes needs antipsychotic treatment and NMS requires stopping antipsychotics immediately, getting the diagnosis right early is a matter of life and death.14PubMed Central. Catatonia versus neuroleptic malignant syndrome: the diagnostic dilemma and treatment
Key clues that favor NMS over catatonia include the presence of very high fever early in the course, extreme muscle rigidity from the start, and markedly elevated creatine kinase levels (a marker of muscle breakdown). Catatonia is more likely when symptoms include waxy flexibility (the person’s limbs stay in whatever position you place them), mutism, staring, and stereotyped movements. But overlap is the rule rather than the exception, and both conditions can coexist in the same patient.15PubMed Central. Malignant Catatonia Versus Neuroleptic Malignant Syndrome
The Lorazepam Challenge Test
When catatonia is suspected, one of the fastest ways to support the diagnosis is the lorazepam challenge test. A clinician gives an intravenous dose of lorazepam (typically around 1 to 2 mg, though some protocols use up to 4 mg) and watches for a rapid improvement in symptoms. In a case series of three catatonic patients, intravenous lorazepam at 4 mg produced quick, optimal improvement.16PubMed Central. Lorazepam challenge test: A unique clinical response in catatonia A patient who has been mute and rigid for hours suddenly beginning to speak and move within minutes of receiving the injection is a powerful diagnostic signal.
There is an important caveat: a positive response strongly supports the diagnosis of catatonia, but a negative response does not rule it out. Some patients with genuine catatonia do not respond to a single lorazepam dose yet still improve with ongoing benzodiazepine treatment over the following days.17PubMed Central. A Case of Pediatric Catatonia: Role of the Lorazepam Challenge Test The test is useful but not definitive on its own, and clinicians need to weigh the full clinical picture.
Treatment When Benzodiazepines Are Not Enough
Benzodiazepines, particularly lorazepam, are the first-line treatment for virtually all forms of catatonia, including drug-induced cases. Most patients respond, and in the alcohol-withdrawal case described earlier, the catatonic symptoms resolved completely with a single injection. But some patients do not respond, or they respond only partially. When that happens, electroconvulsive therapy (ECT) is considered the definitive next step.
ECT in catatonia has response rates ranging from about 80% to 100%, results that are better than for almost any other condition treated in psychiatry.18PubMed Central. Electroconvulsive therapy in catatonic patients: Efficacy and predictors of response It is considered first-line, rather than a last resort, in patients with malignant catatonia, NMS, or catatonic excitement, and in anyone who has not improved adequately with benzodiazepines. Despite this strong evidence, access to ECT for catatonia patients remains limited in many settings due to stigma and legal restrictions.19PubMed Central. Electroconvulsive Therapy for Patients with Catatonia: Current Perspectives One case documented a patient with NMS who failed to respond to standard medical treatment but recovered with ECT, illustrating that it can work even in the most complex, drug-related scenarios.20PubMed. Successful Treatment of Both Refractory Neuroleptic Malignant Syndrome and Subsequent Catatonia With Electroconvulsive Therapy in a Patient With Suspected Kufs Disease
Drug-Induced Catatonia in Children and Adolescents
Catatonia is not just an adult problem, and the drugs that trigger it in young people differ in surprising ways from those in adults. An analysis of the World Health Organization’s global safety database identified 421 pediatric reports of catatonia and found distinct patterns across age groups. In infants, vaccines were the leading reported association. In children aged 2 to 11, the strongest signals came from haloperidol, ondansetron (a common anti-nausea medication), and ciclosporin (an immunosuppressant). In adolescents, antipsychotics dominated, with chlorpromazine, olanzapine, and the anticholinergic drug benztropine showing the highest reporting odds.21PubMed Central. Drug-related catatonia in youths: real-world insights from the WHO Safety Database
The ondansetron finding caught researchers’ attention because it is prescribed so routinely for nausea in pediatric settings that no one would typically think of it as a catatonia risk. The study’s authors specifically highlighted it as a “less suspected” drug. For parents and pediatricians, the practical takeaway is that catatonic symptoms in a child, such as sudden mutism, rigid posture, or repetitive purposeless movements, should prompt a careful review of all current medications, not just psychiatric ones.
Restarting Medications After an Episode
After a drug-induced catatonic episode resolves, clinicians face an uncomfortable question: can the patient ever go back on the class of medication that triggered the episode? For many patients, particularly those with schizophrenia or bipolar disorder, some form of antipsychotic treatment is needed long-term. A case series examining antipsychotic withdrawal-induced catatonia found that gradual reintroduction of antipsychotics after the catatonia had fully resolved led to sustained clinical stability without recurrence.4Industrial Psychiatry Journal. Antipsychotic withdrawal-induced catatonia: A four-case series The key elements were making sure catatonia had completely cleared before restarting, using very gradual dose increases, and emphasizing strict medication adherence going forward to avoid future abrupt withdrawals.
This approach only works with close monitoring. Patients who have had one episode of drug-induced catatonia are considered at higher risk for another, and any re-exposure should happen under conditions where the care team can intervene quickly if symptoms return. In some cases, switching to a different medication within the same class, or moving to a class with a different mechanism of action, is preferable to re-challenging with the original drug.
Why This Condition Still Gets Missed
Catatonia in general is underdiagnosed. Prevalence estimates among acutely ill psychiatric patients range from about 8% to 38%, depending on the setting and the screening tools used.22PubMed Central. Molecular and cellular mechanisms leading to catatonia: an integrative approach from clinical and preclinical evidence The drug-induced subset is harder to pin down because research has historically grouped it with catatonia from other medical causes, making it difficult to isolate and study on its own.9PubMed. Drug-induced catatonia A persistent misconception that catatonia is primarily a feature of schizophrenia also contributes: clinicians may not think to screen for it in a patient who is on steroids for asthma or anticonvulsants for epilepsy.6American Journal of Medicine Open. Catatonia: A Narrative Review for Hospitalists The most common psychiatric causes are actually mood disorders, particularly bipolar disorder and major depression, not schizophrenia.
For people taking any of the drugs discussed here, complete awareness of catatonia as a possible side effect is less important than knowing the general warning signs: sudden inability to speak or move, strange postures held for long periods, repetitive purposeless movements, refusal to eat or drink, or paradoxically extreme agitation with no clear cause. If someone you know develops these symptoms while on medication, or shortly after stopping one, that information is critical to share with the emergency team. The treatment is often straightforward and highly effective, but only if the right diagnosis is made.