Baclofen-Related Mania: Lower Threshold for Bipolar Patients?

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To the Editors
Baclofen, a prototypic γ-amino butyric acid type B receptor agonist that has been in use for more than 50 years for treating spasticity, has recently emerged as a promising pharmacotherapy for treatment of alcohol dependence.1 Initial open and randomized controlled trials have shown the efficacy of 30 mg/d of baclofen on alcohol craving, intake, and relapse prevention.2 Higher doses of baclofen, that is, more than 100 mg/d, have also been used off-label.3 Baclofen-related disinhibition and mania have been reported in a small number of patients being treated for spasticity and dystonia4–7 as well as alcohol use disorders.3,8,9 The doses have varied from 305 to 270 mg/d9 of baclofen, and more than half of the reported cases are in those with a pre-existing bipolar I disorder. We report a case of baclofen-related mania in a patient with bipolar II disorder at a relatively low dose of 20 mg/d. We have applied the Naranjo algorithm10 for establishing causality.
Mr A, a 47-year-old man, presented to our psychiatry outpatient services with complaints of sadness of mood, easy fatiguability, disturbances in sleep and appetite, and decreased self-esteem for the past 2 months. Symptoms fulfilled the criteria for major depression. Around 15 years ago, the patient had a depressive episode of similar severity that lasted for 2 to 3 months and improved on taking some medications. Three years ago, the patient had an episode characterized by euphoria, increased goal-directed activity, overfamiliarity, increased self-esteem, and decreased need for sleep for 2 to 3 weeks, but there was no socio-occupational dysfunction reported. He was started on divalproex 250 mg/d, and thereafter, these symptoms subsided. When improved, his compliance became poor. Mr A had another 2 to 3 such episodes in the past 3 years on the same medication. He was consuming alcohol for the last 19 to 20 years, and a dependent pattern was established for the last 6 to 7 years. Approximately 2 years ago, he reduced both the amount and frequency. He was also using clonazepam 0.25 to 0.5 mg/d for the past 15 years without which he would have sleep disturbances and restlessness. He had never used any other drug of abuse and was never on any other psychotropic medication. To confirm the possibility of bipolar disorder, mood disorder questionnaire11 was applied and he screened positive for the same. As the history revealed episodes of major depression and hypomania, a diagnosis of bipolar II disorder was kept. During the initial period of assessment and management, divalproex 250 mg was continued. The patient continued alcohol intake in the same pattern but stopped clonazepam on his own.
It was suspected that his hypomanic/manic episodes were possibly linked with alcohol intake as increase in alcohol intake usually preceded these episodes. However, the patient desired to consume alcohol occasionally, continued to take approximately 10 to 20 grams of alcohol per day for 3 to 4 days a week, and reported having moderate to severe degree of craving. In view of this, baclofen 20 mg/d was started. On the second day of starting baclofen, Mr A experienced racing of thoughts, appeared extremely cheerful, energetic, confident, boisterous, and argumentative, and had decreased need for sleep. On mental state examination conducted after a week of onset of symptoms, he was euphoric, distractible, with increased psychomotor activity, and had increased self-confidence and self-esteem. Mr A described the new drug (baclofen) as a “wonder drug.” The Young Mania Rating Scale (YMRS) score was 19. He was taking divalproex 250 mg/d with good compliance during this time and had not consumed alcohol since baclofen was started a week ago.
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