High-Dose Baclofen and Mania: What’s the Link?

SAN ANTONIO, TX—Cases of baclofen-indued mania were seen in psychiatric patients receiving the drug for the management of tardive dyskinesia and alcohol dependence, reported Marion E. Wolf, MD, from International Neuropsychiatry Consultants, Highland Park, IL, at the U.S. Psychiatric & Mental Health Congress.

Baclofen, a selective gamma-amino butyric acid type B receptor agonist, is indicated for use in the treatment of neurologic disorders for nearly 50 years. It has been indicated for spasm relief, mainly in spinal cord injury and multiple sclerosis. Baclofen has also been recommended for use in the management of schizophrenia. However, some literature has cited worsening of the psychopathology with the addition of baclofen; a double-blind crossover study of its effects in young chronic schizophrenic patients have shown negative results. 

In 1982, Dr. Wolf reported the first case of mania following the use of baclofen. The patient, a 29-year-old male, had bipolar disorder and severe disabling neck and trunkal tardive dystonia. Baclofen 10mg three times daily was initiated but no improvement was seen at this dose; the patient was titrated up to 90mg daily. Although the patient had significant improvement in dystonia, “he became acutely manic, hyperactive with pressured speech, flight of ideas, grandiosity, and sexual preocccupation,” described Dr. Wolf. 

Another report (Yassa and Iskandar, 1988) documented a case of baclofen-induced mania in a 70-year-old female with bipolar disorder who was treated with baclofen for severe tardive dyskinesia. She was started on baclofen 10mg twice daily and was then increased to 10mg three times daily. However, 2 weeks after the dose increase, “she became irritable, had insomnia, was singing  and laughing inappropriately” and was hospitalized in an acute manic state. 

In 2014, Geoffroy et al. reported a 49-year-old male with a history of alcohol dependence and no previous psychiatric history was treated with baclofen. His dosage was increased to 180mg daily after seeing no reduction in alcohol consumption. One week following the dose increase, his family reported “inflated self-esteem, decreased need for sleep, loquacity, flight of ideas, distractibility, and sexual preoccupation.” 

Recent data from a randomized, placebo-controlled trial (Muller et al., 2015) of high-dose baclofen showed that during the high-dose phase of drug administration, significantly more patients who received baclofen remained abstinent vs. those on placebo (68.2% vs. 23.8%; P=0.014). The high dose in this trial (mean 180mg daily) was “largely responsible for the superiority of baclofen compared to placebo, a result not found in another trial using lower drug dosages.”  

Although some researchers describe a mile safety profile for baclofen with no serious adverse drug events documented in clinical trials, general practice has shown various neuropsychiatric adverse effects (eg, mania, mood disturbances, seizures). Other safety concerns were associated with the intentional overdose of baclofen or to its use with concomitant alcohol or other psychotropic agents, leading to severe toxicity with deep coma and respiratory depression.  

Dr. Wolf noted, “Although baclofen may help many patients with alcohol dependence, its use should be carefully appraised in patients with history of suicidal attempts and/or comorbid psychiatric diagnosis.” High-dose baclofen is still an off-label practice and healthcare professionals need to be aware of risks attendant to its use.