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Missing Tim, thinking of Brenda ... I dedicate this and the following threads to a brave and courageous man.

Unrecognized bipolarity in antidepressant-refractory depression

Clinicians treating patients with depression who fail to respond to adequate antidepressant treatment over a long period of time should consider augmentation therapies and even a bipolar disorder diagnosis, study findings suggest.

Takeshi Inoue and colleagues from the University Graduate School of Medicine in Sapporo, Japan, found that a substantial proportion of patients with antidepressant-refractory depression actually have bipolar disorders.

Moreover, augmenting antidepressant treatment with lithium, L-thyroxine or dopamine receptor agonists proved effective for patients with either unipolar or bipolar antidepressant-refractory depression.

The researchers explored the long-term outcome of 26 antidepressant-refractory patients with depression who had been assessed and treated by the team in 1995.

Before being classified as not responding to treatment, the patients had received at least two tricylic or heterocyclic antidepressants, at a minimum of the equivalent of 150 mg of imipramine for 4 weeks.

In 1995, 21 of the participants were diagnosed with unipolar depression, while five were diagnosed with bipolar depression.

By 2002, five of the patients originally diagnosed with unipolar depression had their diagnosis changed to bipolar disorder. Thus, the 26 participants consisted of 10 bipolar patients and 16 unipolar depression patients.

Over an average follow-up of 5.7 years, ranging from 1 to 7 years, 13 patients – eight bipolar and nine unipolar – achieved full remission and demonstrated high social functioning, defined as a score of 80 or higher on the Global Assessment of Functioning Scale.

The investigators note that a further four patients initially achieved full remission, but experienced subsequent recurrence of their symptoms. Thus, in total 17 of 26 patients achieved remission at least once during the follow-up period.

Augmentation therapies were effective for seven bipolar patients and nine unipolar patients. The addition of dopamine receptor agonists (bromocriptine or pergolide) to antidepressants was effective in nine of 13 patients. The combination of lithium and dopamine receptor agonists with antidepressants was effective in one patient and the combination of lithium and L-thyroxine with antidepressants was effective in two patients.

The findings indicate that "bipolarity plays an important role in the pathophysiology of a subgroup of patients with antidepressant-refractory depression," Inoue et al write in the Journal of Affective Disorders.

They suggest the use of augmentation therapies for patients with antidepressant-refractory depression both for bipolar and unipolar patients, noting that, in their study, no serious side effects or rapid cycling were observed with such treatment.


Journal of Affective Disorders 2006; Vol 95: pages 61-67