Imipramine Shows Benefits in People With Multiple Somatic Disorders

A low dose of the tricyclic antidepressant imipramine can improve the health of patients diagnosed with multiple functional somatic disorders, according to a study published in the May issue of Lancet Psychiatry.

University of Oxford

Functional somatic disorders are complicated and still mysterious conditions in which patients have disproportionate responses to physical discomfort that impair normal living. Fibromyalgia and irritable bowel syndrome are two of the more well-defined somatic disorders, but sometimes patients experience vague or generalized distressing symptoms that fall under the umbrella of somatic symptom disorder.

These somatic problems often co-occur, which can pose a treatment problem since it may not be known which disorder is the main driver of discomfort.

For this study, led by Per Fink, M.D., Ph.D., a professor of psychiatry at Aarhus University Hospital in Denmark, 138 adults aged 20 to 50 with multiple, chronic somatic disorders were randomized to receive a low dose of imipramine (25 mg to 75 mg daily; antidepressant doses range from 100 mg to 200 mg) or placebo for 10 weeks. Imipramine was chosen since it is commonly used to treat people with a single somatic disorder as tricyclics have pain-relieving properties.

The investigators were careful to exclude patients with a history of a mood disorder or schizophrenia to ensure that the painful symptoms and/or improvements were not a byproduct of depression or treatment.

The primary outcome measure was patients’ overall well-being, as assessed by the patient-reported Clinical Global Improvement (CGI) scale; the patients also reported their physical, mental, and social health in other surveys. The investigators acknowledged that self-reports have limitations, but also noted that clinician-rated pain or symptom scales can reflect arbitrariness as well.

After 10 weeks, over half of the patients taking imipramine reported feeling better or much better, compared with 25 percent of the placebo group. The imipramine group also had far fewer patients reporting symptoms as worse or much worse.

The patients taking imipramine reported significantly higher levels of adverse side effects than the placebo group, which the authors stated might be due to the nature of the somatic syndromes and that patients were more sensitive to side effects that would otherwise have been considered mild. Very few of the participants dropped out, however, perhaps indicating some built-in tolerance to discomfort.

Among the secondary measures, the imipramine group reported better outcomes on their physical functioning than the placebo group, but not on their mental health or social outcomes. This finding suggested that imipramine did not improve some subclinical depression.

At the same time, the boost from imipramine “was not exclusively attributable to pain relief, because those patients who did not report pain as their predominant symptom also had an overall health improvement,” Fink and colleagues wrote.

Michael Sharpe, M.D., a professor of psychiatry at the University of Oxford and a specialist in the psychiatric aspects of medical illness, thinks it is logical that imipramine would do more than just ease pain.

“Some people may define these syndromes as the body working out of tune, but it’s actually the brain that is responding inappropriately, and the goal is to reset that brain-body communication,” he told Psychiatric News.

Sharpe, who was not involved in this study, clarified that he does not support the notion that these somatic problems are purely mental (“it’s all in your head”); rather, these are physical symptoms with a strong brain component.

He also cautioned against extrapolating these findings to suggest that imipramine or other tricyclics would offer a two-for-one benefit in patients with diagnosed depression and strong somatic symptoms. “It’s a matter of opinion, but you should treat the depression first,” he said.

This study was supported by Trygfonden, a Danish foundation, and Takeda Pharmaceuticals provided the imipramine. ■