The onset and temporal course (episodic vs continuous) of depressive and anxiety symptoms and the influence of stressors on these factors help formulate the diagnosis and plan the management. The cost and availability of treatments, illness severity, presence of comorbid medical conditions, and past/family history of response to a particular treatment will also influence the choice of pharmacotherapy. In addition, an inquiry into the patient’s functional state and assessment of disabilities is useful in monitoring improvement and progress. (Table 1 provides clinical tips for treating comorbid depression and anxiety disorder.)
After evaluation, an appropriate explanation of the comorbid condition to patients is vital. Patients are often given information on depression that pertains only to its classic presentation, with no consideration of the anxiety component, which is often more troublesome to the patient. Information on the complexity of the depression-anxiety presentation and the need for effective treatment can significantly improve adherence.
In addition to pharmacotherapy, psychological (specifically, cognitive-behavioral therapy) and social interventions should form an important component of the overall management. However, only pharmacological options are discussed in this review.
Psychopharmacology
Many psychotropic agents have been investigated for the treatment of individual depressive and anxiety disorders. However, specific trials in depression with comorbid anxiety disorders are limited. While antidepressants, particularly SSRIs and serotonin norepinephrine(Drug information on norepinephrine) reuptake inhibitors (SNRIs), form the bulk of the recent treatment literature, there is increasing evidence of the benefit of atypical antipsychotics, anticonvulsants, and benzodiazepines in optimizing treatment response.
SSRIs and SNRIs. SSRIs, which include fluoxetine(Drug information on fluoxetine), fluvoxamine(Drug information on fluvoxamine), sertraline(Drug information on sertraline), paroxetine(Drug information on paroxetine), citalopram, and escitalopram(Drug information on escitalopram), have a proven history of efficacy in the treatment of patients with discrete depressive and anxiety disorders. In general, this class of agents appears to be effective in treating depression with comorbid anxiety disorders.3 SSRIs are generally well tolerated, although they do have potentially troublesome adverse effects, such as sexual dysfunction and agitation, as well as GI effects.
SNRIs include venlafaxine, duloxetine(Drug information on duloxetine) and, more recently, desvenlafaxine. There is some evidence that remission rates may be higher with venlafaxine than with SSRIs.4 Furthermore, higher than normal doses of venlafaxine may have an advantage for patients with refractory depression, who often have comorbid anxiety disorders.5 No efficacy advantage for duloxetine or desvenlafaxine over SSRIs has been reported; this is probably because of their relatively recent introduction to the psychiatric pharmacopeia. A suggested schedule for treatment with antidepressants is given in Table 2.
Tricyclic antidepressants, monoamine oxidase inhibitors, reversible inhibitors of monoamine oxidase. These classes of antidepressants are effective for depressive disorders but tend to have a greater burden of adverse effects than the current first-line agents. Potential sequelae include risk of toxicity with overdose of tricyclic antidepressants (TCAs), dietary restrictions with monoamine oxidase inhibitors (MAOIs), and a greater likelihood of drug-drug interactions with both classes of agents.6 Several TCAs, such as clomipramine(Drug information on clomipramine) and imipramine, have been shown to be effective in anxiety disorders and in depression comorbid with anxiety disorders.7,8 Similarly, MAOIs (eg, phenelzine(Drug information on phenelzine)) and reversible inhibitors of monoamine oxidase (RIMAs), eg, moclobemide(Drug information on moclobemide), have shown efficacy in depressive disorders and in anxiety syndromes—particularly social anxiety disorder (SAD) and posttraumatic stress disorder (PTSD)—although RIMAs are not currently available in the United States.9
Other novel antidepressants. Bupropion, a norepinephrine dopamine(Drug information on dopamine) reuptake inhibitor, has a different adverse-event profile from SSRIs. Meta-analyses confirm that its efficacy is equal to that of SSRIs in depressive disorders and even for anxiety symptoms associated with depression, although similar benefits were not seen in primary anxiety syndromes.10-12
