Clozapine for Treatment-Resistant Bipolar Disorder: A Pilot Randomised Controlled Trial

A Phase II pilot randomised controlled trial

THE RATIONALE

Why this study?

Bipolar disorder can be severe, and for many people symptoms continue despite standard treatment. Clozapine is widely used for treatment-resistant schizophrenia and is recommended in some guidelines for treatment-resistant bipolar disorder. It has never been tested against a placebo in this group. This pilot study will find out whether a larger trial is practical and whether clozapine can be given safely and tolerably alongside a mood stabiliser.

THE STUDY

Study at a glance

Phase II pilot, randomised, double-blind, placebo-controlled

Adults aged 18–65 with bipolar I disorder who have not responded adequately to standard treatment and are still experiencing symptoms

Two psychiatric centres in Pakistan (Karachi and Hyderabad)

40 participants, with 20 receiving clozapine and 20 receiving placebo

Clozapine or an identical-looking placebo, added to each participant’s usual mood stabiliser, with the clozapine dose increased gradually

12 weeks of treatment with weekly assessments

How easy the study is to run (recruitment, retention, adherence), safety and tolerability, and early signs of change in mood, anxiety, suicidal thoughts and daily functioning

Participant allocation

40 participants in two groups - 20 clozapine & 20 placebo

Study overview

Gradual clozapine dose increase -> Weekly assessments -> 12-week treatment period

PARTICIPANT MONITORING

Keeping participants safe

Participants are monitored closely, with regular blood tests, heart checks, side-effect reviews and suicide-risk assessments. An independent committee oversees safety throughout the study.

Regular blood tests

Heart checks

Side-effect reviews

Suicide-risk assessments

Independent committee oversight