Major depressive illness is a common disorder with a lifetime prevalence of at least 20% in women and 10% in men (26). It has been characterized as “the neglected major illness” because of the consistent underrecognition of the disorder and the tremendous costs it engenders (an estimated $44 billion annually in the United States) (18). The lion’s share of the cost of depression is a consequence of inadequate recognition and care of the illness, leading to lowered employment productivity. Although it can be a lifelong disorder, the majority of patients with depression can be treated successfully (1,18). On the other hand, efforts to manage head pain are considerably less likely to succeed if comorbid depression is not recognized and effectively treated.

The hallmark of major depressive illness is sad or depressed mood and a loss of interest or pleasure in previously enjoyed activities (anhedonia). The syndrome of depression is defined by a collection of symptoms that includes depressed mood and also results in significant functional impairment (see Table 137-1). Not everyone who is depressed experiences every symptom, with some patients experiencing only few symptoms and others many. The severity of symptoms varies considerably both between individuals and within patients over time. Depressive illness has a high rate of comorbidity with anxiety disorders and substance abuse.

Although full-blown depression with depressed affect, tearfulness, and psychomotor symptoms is not difficult to
diagnose, depression may not always be evident without systematic inquiry. Inquiry about all of the symptoms that constitute the criteria for major depression is essential for accurate diagnosis of depression.

Pharmacologic treatment of major depression focuses on the use of adequate doses of antidepressants. Tricyclic and related cyclic antidepressants (TCAs) can be effective in the prophylaxis of headache disorders (17,45), but they are now less often used in treatment of depression because of side effects associated with the high doses required to achieve an adequate clinical response. The newer selective serotonin reuptake inhibitors (SSRIs) have fewer side effects (e.g., less sedation, less likely to cause weight gain) than TCAs and have a lower risk for overdose. There is, however, less evidence of the effectiveness of fluoxetine and other SSRIs (e.g., fluvoxamine, paroxetine, sertraline, venlafaxine) for the prophylaxis of migraine and TTH (8,17,27,45). An SSRI may be worth considering if a tricyclic drug is poorly tolerated or has proved unsuccessful.

Because the overall efficacy of antidepressants does not vary dramatically from one medication choice to the next (within a class), the medication choice should be based on side effect profile and symptom target. For example, TCAs would be preferred for a patient with insomnia, while an SSRI might be preferred for an overweight or obese patient. SSRIs and TCAs are contraindicated when mania is present or suspected. The anticonvulsant valproate is effective in treating migraine and comorbid manic depression (bipolar disorder). The β-blockers, typically used in migraine prophylaxis, are relatively contraindicated when depression is also present. Researchers recently have begun to evaluate the benefits that may be achieved through use of an algorithmic approach to prescribing medications for patients with comorbid headache and psychiatric illness. Kaniecki (25) implemented an algorithm calling for use of SSRIs for migraineurs with depression and anxiety, TCAs for those with insomnia, and antiepileptic drugs (AEDs) for the remaining patients. Approximately two thirds of 367 patients experienced significant reductions in headache frequency and disability at 1 year, leading Kaniecki to conclude that the presence of these comorbidities may help rationally guide the selection of preventive agents for patients with migraine. Table 137-2 offers an overview of the therapeutic opportunities and limitations in treating comorbid migraine and psychiatric disorders.

The U.S. Agency for Healthcare Research and Quality (1) has developed guidelines for treating major depression. Once a diagnosis has been made, treatment should be monitored every few weeks. Response to treatment should be assessed at week 6, and if the patient shows clear improvement the treatment should be continued for an additional 6 weeks. If there is complete remission of symptoms, medication is continued for 4 to 9 months to prevent relapse. Maintenance treatment should be considered because after one episode of depression, the chance of recurrence is at least 50%. Increasing evidence supports ongoing treatment for a period of several years, if not indefinitely, to reduce the likelihood of relapse and recurrence. If a patient is only somewhat better at 6 weeks, a dose adjustment can be made. Treatment should be continued and monitored every 2 weeks. If at week 12 there is not a complete response to medication, a referral for psychotherapy, a referral to psychiatry for medication management, or a change in medication should be considered, although it may be more efficacious to augment SSRI antidepressant medication with bupropion than to switch SSRIs (34).