Can antipsychotics worsen psychosis?

Can Antipsychotics Worsen Psychosis?

Yes, antipsychotics can worsen psychosis in certain circumstances, particularly through mechanisms like dopamine supersensitivity psychosis, which can develop with long-term use and lead to tolerance, rapid relapse upon discontinuation, and treatment resistance. 1

Mechanisms of Antipsychotic-Induced Worsening of Psychosis

• Long-term administration of antipsychotics can upregulate D2 receptors and produce receptor supersensitivity, leading to behavioral supersensitivity to dopamine stimulation 1
• This supersensitivity can manifest as supersensitivity psychosis (SP), which occurs in approximately 30% of patients with schizophrenia and up to 70% in treatment-resistant schizophrenia 1
• Antipsychotic-induced SP was first characterized by four clinical features:
  • Rapid relapse after drug discontinuation, dose reduction, or switching antipsychotics
  • Tolerance to previously observed therapeutic effects
  • Co-occurring tardive dyskinesia
  • Psychotic exacerbation triggered by life stressors 1

Clinical Presentations of Worsening Psychosis

• Patients may experience breakthrough psychotic symptoms despite previously effective treatment, indicating tolerance development 1
• Abrupt discontinuation or significant dose reduction can trigger rapid and severe psychotic relapse, often more intense than the original symptoms 1
• Psychotic symptoms may emerge alongside movement disorders like tardive dyskinesia, suggesting a common underlying mechanism of dopamine supersensitivity 1
• In dementia patients, antipsychotics provide at best small benefits for psychosis while carrying significant risks, including potentially worsening behavioral symptoms 2

Risk Factors for Antipsychotic-Induced Worsening

• Long-term use of high-potency antipsychotics 1
• Rapid titration or excessive initial dosing, which can increase side effects without improving efficacy 3
• Switching between antipsychotics with different pharmacodynamic profiles without proper cross-titration 3
• Use of antipsychotics in vulnerable populations (e.g., elderly with dementia) where risk-benefit ratio is less favorable 2

Management Strategies to Prevent Worsening

• Start with low doses and titrate slowly to minimize side effects while achieving therapeutic benefit 3
• For first-episode psychosis, use appropriate initial target doses (e.g., risperidone 2 mg/day or olanzapine 7.5-10.0 mg/day) 3
• Avoid excessive initial dosing as it doesn't hasten recovery but increases side effects 3
• Implement treatment for 4-6 weeks using adequate dosages before determining efficacy 3
• Monitor closely for extrapyramidal side effects, which may be early indicators of developing dopamine supersensitivity 3

When to Consider Changing Treatment Approach

• If no response after a 4-week trial of an adequate dose, the medication should be tapered and withdrawn 2
• If positive symptoms persist after trials of two first-line atypical antipsychotics (around 12 weeks total), review reasons for treatment failure 3
• For treatment-resistant cases, consider clozapine, which has a different mechanism of action and may be effective where other antipsychotics have failed 3
• In patients with dementia experiencing psychosis, carefully weigh risks and benefits, as antipsychotics have limited efficacy and significant adverse effects in this population 2

Important Caveats and Pitfalls

• Avoid abrupt discontinuation of antipsychotics, which can trigger withdrawal syndromes and rebound psychosis 1
• Don't neglect monitoring for movement disorders, which may signal developing dopamine supersensitivity 3, 1
• Be aware that what appears as treatment resistance may actually be antipsychotic-induced supersensitivity psychosis 1
• Remember that schizophrenia itself carries risks for various medical conditions independent of medication effects, so decisions should balance disease risks against medication risks 4