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Benzodiazepine reduction without withdrawal symptoms possible in patients with schizophrenia, bipolar disorder


 

AT THE INTERNATIONAL CONGRESS ON SCHIZOPHRENIA RESEARCH

References

COLORADO SPRINGS – Patients with schizophrenia and bipolar disorder can reduce or even discontinue their reliance on benzodiazepines when kept to a gradually tapered titration, results of a Danish study have shown.

Benzodiazepines often are prescribed to patients with severe mental illnesses to help relieve comorbid anxiety and insomnia. According to Dr. Lone Baandrup, a researcher at the Center for Neuropsychiatric Schizophrenia Research at the Copenhagen University Hospital in Glostrup, Denmark, the treatment is usually meant as a temporary measure during acute episodes, but patients often become addicted.

Dr. Lone Baandrup Whitney McKnight/Frontline Medical News

Dr. Lone Baandrup

Dr. Baandrup said in an interview at the biennial meeting of the 15th International Congress on Schizophrenia Research that because it is well established that patients with severe mental illness often suffer from a diminished ability to secrete endogenous melatonin, “we wanted to see if we could facilitate tapering patients off their benzos using a prolonged-release melatonin.”

Dr. Baandrup and her colleagues randomly assigned 86 adults with a diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder who had been on a daily regimen of an antipsychotic and at least one benzodiazepine derivative for at least 3 months, to receive either prolonged-release melatonin 2 mg daily or matching placebo. In the intention-to-treat analysis, each group was guided by a caregiver to gradually taper their respective daily benzodiazepine dosage.

Participants were examined at baseline and at 8, 16, and 24 weeks, and were monitored weekly by telephone. All participants, researchers, treating clinicians, and outcome assessors were blinded to group assignment.

No significant difference was found between the groups as to mean benzodiazepine dosage at 24 weeks, the study’s primary outcome, but the placebo arm had a greater reduction in benzodiazepine dosage (8.01 mg in the study arm vs. 5.72 mg in placebo; difference between means, –2.29; 95% confidence interval, –5.78-1.21; P = .20).

Nearly half of the placebo group achieved complete cessation of benzodiazepine use, compared with more than one-third of the study group (21 out of 44 vs. 16 out of 42; odds ratio, 0.64; 95% confidence interval, 0.26-1.56; P = .32).

Serious or nonserious adverse events were similar across the groups.

A separate analysis of the data not presented at the conference as to whether melatonin had any effect on subjective sleep measures showed that those in the melatonin group had improved sleep according to the Pittsburgh Sleep Quality Index. When compared with the control group, “the difference was about 2 points, so it was only on the border of clinical significance, but their sleep did not get worse,” Dr. Baandrup said.

The investigators also used the Pittsburgh Sleep Diary to measure whether there were any objective differences in sleep between the melatonin and placebo groups, and found that reducing benzodiazepine use did not result in insomnia. “It remained the same from baseline to follow-up," Dr. Baandrup said. “Many patients are afraid to taper off their benzos because they fear their sleep will worsen, but we didn’t find that.”

Dr. Baandrup did not have any relevant disclosures.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

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