For patients with depression and comorbid OCD, treatment often begins with an SSRI. Some advantage has been suggested for sertraline and fluvoxamine. The dosage is gradually increased based on tolerability. Clinicians should also expect an extended treatment period (6 to 12 months or more) with the likelihood of maintenance treatment for many patients.64

Combination of SSRIs or clomipramine with atypical antipsychotics (eg, risperidone) is a common strategy for treatment-resistant patients. Comorbid OCD and bipolar disorder is particular- ly hard to treat because maintenance with anti- obsessive agents is needed for OCD, which may make patients vulnerable to manic switches, thus necessitating antimanic prophylaxis.65

PTSD is often comorbid with depression, other anxiety disorders, personality disorders, and/or substance abuse, which makes treatment a challenge.66 As with most other anxiety disorders, there are no studies specifically on depression with comorbid PTSD, although many PTSD trials do permit inclusion of comorbid depression.

As such, several classes of antidepressants have shown efficacy for PTSD in the presence of significant depressive symptoms. Most evidence has been for SSRIs and venlafaxine.66 Mirtazapine, moclobemide, phenelzine, and adjunctive atypi-cal antipsychotics have reasonable evidence to support their benefit.19,66-68 When symptoms are refractory, TCAs, adjunctive anticonvulsants (particularly for psychotic PTSD symptoms), buspi­rone, and the opioid receptor antagonist, naltrexone, could be considered.66,69,70 Monotherapy with benzodiazepines has not been found to be of benefit in PTSD, but these agents may be useful when combined with SSRIs.66

Treatment of depression and comorbid PTSD should be long-term because of the likelihood of relapse with early discontinuation.71 Delayed onset of improvement and lag in improvement in psychosocial functioning further support longer maintenance treatment.71

Conclusion
Comorbid depressive and anxiety disorders are commonly seen in both primary care and the specialty setting. Such comorbidity can present as major depression with subsyndromal anxiety symptoms or unipolar/bipolar depression comorbid with an anxiety disorder. Those patients with depression and comorbid anxiety appear to have a significantly greater illness burden, worse response, and a more chronic course of illness than patients with depression alone. While most antidepressants have been shown to have significant anxiolytic properties, there are few systematic investigations of their benefit in depression with comorbid anxiety disorders. Support for their use comes largely from studies of non-comorbid populations with primary anxiety. Overall, SSRIs and SNRIs continue to remain the first-line agents for the treatment of depression comorbid with anxiety disorders. Short-term benzodiazepine augmentation may help many patients, and there is preliminary evidence for the benefit of atypical antipsychotics as well as certain anticonvulsants.

In resistant and refractory cases, augmentation and combination strategies with these agents may be warranted. Should one condition remit and the other persist, specific interventions for the residual condition should be considered; affected patients often need longer maintenance treatment (Table 5). Both the literature and clinical experience suggest that a combination of pharmacological and psychological forms of treatment is ideal. Remission of both clinical syndromes should be the goal.
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