Saying No to Cannabis Improves Bipolar Outcomes

Kenneth Bender

January 29, 2015

Bipolar patients with mania/mixed episodes who quit using cannabis do better than their counterparts who continue using the drug, new research shows.

Investigators at the International Mood Disorders Research Center, Centro de Investigacíón Biomédica en Red en Salud Mental (CIBERSAM), in Spain, found that quitting cannabis during acute treatment for manic/mixed bipolar episodes and refraining from use during a maintenance treatment period significantly improved function and lowered the risk for recurrence.

"Our findings indicate that the negative effects of cannabis use on the course of bipolar disorder disappear when patients stop using it: We found that patients who stopped using cannabis during an acute manic/mixed episode had similar clinical and functional outcomes at 2 years as those who have never used cannabis," the researchers, led by Ana Gonzales-Pinto, MD, PhD, Division of Psychiatry Research, Santiago Apostol Hospital, Vitoria, Spain, write.

"Our results also showed that patients who continued to use cannabis had worse outcomes than those who either stopped using cannabis or had never used it," the researchers add.

The study was published in the February issue of the Acta Psychiatrica Scandinavica.

First Long-term Look

High rates of use of cannabis and other recreational/illicit drugs in patients with bipolar disorder are well documented. In addition, previous research suggests that cannabis has a deleterious effect on the course of the illness. However, the investigators note that the current study, known as the the European Mania in Bipolar Longitudinal Evaluation of Medication (EMBLEM) study, is "the first to explore the long-term consequences of continuation or cessation of cannabis use on remission, recovery, recurrence, and relapse in patients with bipolar disorder."

The researchers analyzed the course of bipolar disorder in 1922 patients from various centers in 14 European countries who had either stopped using cannabis during acute treatment of mania or mixed state episode, were not users, or who had continued to use the drug.

Patients had progressed from a 12-week acute treatment phase to a maintenance phase extending for 24 months from baseline. Treatments were consistent with usual practice, including antipsychotic and mood stabilizers given singly or in combination and with modifications in regimen and dose as clinical circumstances required.

Severity of illness was assessed at each visit with the Clinical Global Impression–Bipolar Disorder Scale and in the acute phase with the Young Mania Rating Scale and the 5-item version of the Hamilton Depression Rating Scale.

Functional outcomes were judged from capacity to maintain vocation, relationships, and living situations. Clinical outcomes were reflected in remission, recovery, recurrence, or relapse.

Of the 1922 patients, 132 (6.9%) continued cannabis use, 89 (4.6%) stopped use prior to the maintenance phase, and 1701 (88.5%) were not cannabis users.

The investigators used logistic regression models to determine association between cannabis use and the clinical and functional outcomes; they controlled for alcohol and other substance use as potential confounding variables.

Higher Rate of Recurrence

Continuing to use cannabis vs refraining from using the drug throughout the maintenance treatment phase or having no previous use was associated with lower rates of remission and recovery and higher rates of recurrence.

When alcohol and other substance use was factored into the analysis, cannabis remained differentiated for reducing time to, and increasing frequency of, symptom recurrence but was not statistically distinct from other substances on the association with lower rates of remission and recovery.

In addition, Dr Gonzales-Pinto told Medscape Medical News that "patients that continued using cannabis had more suicide attempts than those that quit or those who never used cannabis."

Nine of 130 patients (6.9 %) who continued using cannabis attempted suicide during the maintenance phase, in comparison with 51 of the 1701 nonusers (3.0 %) and 4 of 90 (4.4 %) who had quit using.

"In the future, investigations about the benefits of quitting cannabis should be conducted in younger patients, as they use cannabis more frequently," said Dr Gonzales-Pinto.

"It would also be of interest to examine the association of cannabis with depressive symptoms and its effect on medication adherence," she added.

According to the investigators, the study's findings "imply that stopping cannabis use is an important goal to achieve in cannabis users with bipolar disorder."

Clinical Implications

Commenting for Medscape Medical News, Steven Marwaha, PhD, MRCPsych, associate clinical professor of psychiatry, University of Warwick, United Kingdom, who is also the coauthor of a recently published meta-analysis that linked cannabis use to exacerbation of manic symptoms, said the research points to the need for cannabis cessation in patients with bipolar disorder.

"The main clinical implication may be that we need to help patients quit cannabis, as their outcomes may then be the same as if they never used," he said.

Although characterizing the treatment of comorbid drug use in patients with severe mental illness as "notoriously difficult," Dr Marwaha said that "trials of innovative approaches such as contingency management are under way and may give clinicians critical guidance on helping this group to quit cannabis and thus improve their outcomes."

A complete list of the investigators' disclosures can be found in the original study. Dr Marwaha reports no relevant financial relationships.

Acta Psychiatr Scand. 2015:131:100-110. Abstract

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