01. Catatonia: Should Antipsychotics Always Be Avoided?

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Antipsychotics in Catatonia: Risks and Benefits

Antipsychotics are bad for catatonia. Chances are you’ve heard this message before. You may have even heard this message from me. We’ve known this for a long time at least since the ’80s when cases of neuroleptic malignant syndrome began to be reported more commonly. People started to recognize that NMS had a lot of similarities to malignant catatonia.

But absolutes are tricky in psychiatry. Sometimes, we feel compelled to use antipsychotics in catatonic patients, usually when they also have prominent psychosis.

To complicate matters further, there are dozens of case reports of second-generation antipsychotics successfully treating catatonia. It’s common enough that we included atypical antipsychotics in our 2017 catatonia treatment algorithm, albeit with many caveats and only as a last resort.

So what’s the best practice for antipsychotics and catatonia? Let’s examine a recent systematic review that provides some guidance.

Historical Context and Current Guidelines

Though typical antipsychotics were historically used in the treatment of catatonia throughout the ’60s and ’70s prior to the discovery that benzodiazepines are highly effective at treating catatonia, they have generally fallen out of favor in the past three to four decades. This is largely because of recognition that antipsychotics can induce or worsen catatonia including precipitating malignant catatonia and/or neuroleptic malignant syndrome.

Nonetheless, discussion of the use of antipsychotics is included in:

• The Maudsley Prescribing Guidelines for Catatonia which specifically names olanzapine and clozapine
• The British Association for Psychopharmacology Guidelines for Catatonia
• The recently published APA resource document on catatonia

Two Clinical Situations Requiring Consideration

Despite their usage being more controversial these days, the question of whether it is appropriate to try an antipsychotic continues to arise in two distinct situations related to the treatment of catatonia.

• When treating catatonia and psychosis/agitation simultaneously
• For treatment-resistant catatonia when other recommended agents have failed

Recent Systematic Review Examines 175 Antipsychotic Trials

The systematic review we’re focusing on today was recently published in the journal European Psychiatry. The authors ultimately included 79 articles involving 175 antipsychotic trials in 100 patients. Most of these were case reports or case series.

Here’s a key point: only 41% of patients had received a benzodiazepine prior to the antipsychotic.

That’s strikingly low, considering that benzodiazepines are the gold standard. It might reflect a sample skewed toward schizophrenia, a condition where catatonia is considered less benzodiazepine-responsive. Indeed, the authors report that nearly 2/3 of patients in the review had psychotic disorders.

Success Rates May Reflect Publication Bias

The main finding of the review is that antipsychotics were useful for catatonia in 60% of trials but harmful in 10%. The authors acknowledged the importance of considering the bias of case report literature. Cases reporting a successful outcome are much more likely to be written and published.

Selection bias would also influence the cases in which antipsychotics were tried in the first place. In other words, the reader should definitely not assume that antipsychotics would be useful in 60% of all cases of catatonia and only harmful in 10% of all cases.

It’s also notable that over a third of trials and nearly 50% of beneficial trials reported in this review involved co-administration of benzodiazepines. This would seemingly make it challenging to separate the effects of the antipsychotics from those of the benzodiazepines.

Agent-Specific Outcomes Vary Significantly

One of the more interesting findings of the review involves breaking the cases down by agent used. The authors note that:

• Cases tended to have positive results when involving amisulpride, clozapine or risperidone
• Cases tended to have equivocal results when involving aripiprazole or olanzapine
• Cases tended to have detrimental results when involving haloperidol and quetiapine

I found this really interesting because it differs from what we found when we did our review of all alternative medications in 2017. At that time, aripiprazole along with clozapine actually had the most positive case reports of any antipsychotic. Olanzapine was a close third just ahead of risperidone.

Mixed Evidence For Individual Agents

Thinking about olanzapine specifically, the authors here note that there are a couple of studies that have suggested that olanzapine might work well for patients with schizophrenia and catatonia. But they also point to a retrospective study from McLean Hospital showing decidedly mixed results for olanzapine.

They also note that interestingly risperidone was compared to ECT in a double-blind randomized controlled trial in lorazepam-resistant patients with schizophrenia and catatonia. Not surprisingly, ECT significantly outperformed risperidone, but both groups did see reductions in Bush-Francis scores without adverse outcomes over three weeks.

In other words, data on all of these agents seem somewhat mixed.

Practical Guideline: When Antipsychotics May Be Justified

When considering antipsychotics use in catatonia:, one case is relatively straightforward: catatonia after abrupt clozapine discontinuation. In these situations, reinitiating clozapine is clearly supported by the literature and appears to be the best course of action.

Otherwise, I generally avoid antipsychotics in catatonia—unless there’s intractable psychosis disrupting care, or all other options have been tried and failed.

If you do find yourself in that situation, here are three principles I follow:

• Use a low-potency agent. The review emphasized avoiding first-generation antipsychotics, but I think potency matters more than generation. High-potency agents, like risperidone, raise red flags for me due to higher NMS risk. Clozapine seems to be emerging as perhaps the best choice both in terms of safety and efficacy. Despite mixed data, I would still consider aripiprazole or olanzapine, and maybe even chlorpromazine—it’s low potency, available in multiple forms, and can be paired with benzos if you need parenteral administration.
• Start low and go slow. Use the lowest effective dose and titrate gradually.
• Always co-administer with a benzodiazepine. Give both agents at the same time. This is probably the most important strategy to mitigate risk of worsening catatonia or malignant progression.

Conclusion: Balancing Caution and Flexibility

This review adds to our understanding of a complex issue. It encourages caution with antipsychotics in catatonia but acknowledges that flexibility is sometimes needed for optimal patient care.

As prescribers, we can’t be too dogmatic or have too many “nevers.” We must balance the risks and potential benefits in each individual case, always prioritizing patient safety and well-being.

Abstract

The use of antipsychotics in the treatment of catatonia: a systematic review

Maximilien Redon, Jordan Virolle, François Montastruc, Simon Taïb, Alexis Revet, Julien Da Costa & Etienne Very

Background
Catatonia in psychotic patients presents unique challenges. While antipsychotics are the cornerstone of schizophrenia treatment, their use in catatonic patients is sometimes discouraged for fear of worsening the signs. Reports on the successful use of second-generation antipsychotics have been published. We conducted a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines to describe the outcomes of antipsychotic-treated catatonic events.

Methods
We searched Medline and Web of Science databases from 2000 to 2023 using search terms including “catatonia” and “antipsychotic agents” for all original peer-reviewed articles, including clinical trials, observational studies, and case-reports. We included antipsychotic-treated catatonic events and extracted data on patient characteristics, pharmacological context, agent involved, and treatment outcomes for each antipsychotic trial.

Results
After screening 6,219 records, 79 full-text articles were included. Among them, we identified 175 antipsychotic trials (in 110 patients). Only 41.1% of the patients benefited from a previous benzodiazepine trial. Antipsychotic use was considered beneficial in 60.0% of the trials, neutral in 29.1%, and harmful in 10.9%. Trials tended to be reported as beneficial for amisulpride, clozapine, and risperidone, equivocal for aripiprazole and olanzapine, and mostly detrimental for haloperidol and quetiapine. Psychotic disorders were the most common underlying etiology (65.8%).

Conclusions
Antipsychotics could be an option in the treatment of catatonia in psychotic patients. However, with few exceptions, we found non-beneficial outcomes with all second-generation antipsychotics in varying proportions in this largest review to date. Although olanzapine is widely used, it is associated with mitigated reported outcomes.

Reference

Redon, M., Virolle, J., Montastruc, F., Taïb, S., Revet, A. Da Costa, J & Very,E. (2025). The use of antipsychotics in the treatment of catatonia: a systematic review. European Psychiatry. 2025;68(1):e48.