Question:How do you treat a bipolar patient who complains about chronic periods of depression, when the depression does not meet the DSM-IV criteria for major depression?

Reply from S. Nassir Ghaemi, M.D., M.P.H.

This is, in fact, the scenario for most patients with bipolar disorder. Recent data show that patients diagnosed with bipolar disorder spend about half their lives with chronic subsyndromal depression (1). Most people do not realize that this kind of chronic subsyndromal depression is generally the result of treated bipolar disorder, treated with our best current medications, and not untreated natural history. This then is the biggest morbidity and treatment challenge that we face.

The best approach varies on the basis of the previous course of illness and past treatment response, as well as the current treatment being given. A few scenarios are possible:

The patient has bipolar disorder and is not taking any proven mood stabilizers (lithium, lamotrigine, divalproex, or carbamazepine) but has subsyndromal depressive symptoms.

In this case I would begin one of those proven mood stabilizers; following APA treatment guidelines (2) and randomized evidence, one might lean toward lithium or lamotrigine. If, as is frequently the case, the patient is taking other medications such as antidepressants and/or antipsychotics, I would also recommend discontinuing those agents and simply instituting a single proven mood stabilizer as above. This recommendation may seem counterintuitive because anti-depressants are supposed to treat depression and some antipsychotics, like quetiapine, are now indicated for bipolar depression (3). But all such data are for the acute phase, i.e., for about 2 months of treatment when the patient is currently depressed. Usually the scenario is that the patient was acutely depressed 9 months ago, received treatment such as quetiapine plus citalopram [or another serotonin reuptake inhibitor (SRI)], improved partially, and now has chronic subsyndromal depression. None of these agents, in contrast to lamotrigine or lithium or even divalproex, have been shown to have long-term benefits in the prevention (as opposed to treatment) of depressive symptoms in bipolar disorder. Most antipsychotics have simply not been studied in maintenance treatment of bipolar disorder, and those that have been studied, such as olanzapine or aripiprazole (despite Food and Drug Administration indications), have not clearly been shown to be beneficial in depression prevention. Antidepressants, in contrast, have repeatedly been studied and have failed to have preventive benefits for depression in bipolar disorder (4). Most of the data are for tricyclic antidepressants, but randomized data for SRIs are emerging, which suggest either little or no long-term benefit for depression prevention (5). In other words, both antidepressants and antipsychotics seem to have short-term but not long-term benefits. One needs to use the proven mood stabilizers for long-term benefits.

The patient has bipolar disorder, is taking a proven mood stabilizer as above, and is also taking an antidepressant, but has chronic subsyndromal depression.

Again, in this case, I would begin by stopping the antidepressant, because antidepressants have been associated with rapid cycling and worsening of mood episodes and even chronic irritability with depression in some patients (possibly around 25% of patients) (6). I would replace the antidepressants with other mood stabilizers or atypical neuroleptics or novel anticonvulsants.

The patient has bipolar disorder, is taking a proven mood stabilizer as above, and is not taking an antidepressant, but has chronic subsyndromal depression.

In this case, I would still add other mood stabilizers, or atypical neuroleptics, or novel anticonvulsants to try to improve the depressive symptoms. I would also recommend and try to arrange adjunctive psychosocial interventions, such as cognitive behavior therapy, group psychoeducational psychotherapy, and/or advocacy-based support groups (7). In my experience, although these treatments are much better proven long-term treatments in bipolar disorder than antidepressants, many clinicians and patients ignore or undervalue them. Their practicality can be a problem (cost, lack of insurance coverage, time involved, and availability of trained therapists); this is why the support groups can be so important.

A final scenario is that the patient may not have subsyndromal depression at all but rather a kind of existential despair that we interpret, within our biological mindsets, as major depressive symptoms (8).

In this case, the issue is dealing with all the losses of the past, and the need for long-term treatment with multiple medications with side effects and readjusting to a new life with a treated illness. Here both the therapeutic alliance between the psychiatrist and patient is important, as well as a good individual psychotherapy relationship in which the therapist concentrates on simply being there with the patient. Over time, often a long time, such symptoms then begin to gradually resolve.