Depression and Comorbid Anxiety: An Overview of Pharmacological Options

Mirtazapine, a noradrenergic and selective serotonin antidepressant, is said to be particularly effective in severe depression, with comparable efficacy to TCAs and the advantage of enhancing sleep and appetite.¹³ There is evidence of its bene­fit in depression comorbid with anxiety disorders, as well as with specific anxiety syndromes.^14,15

Buspirone, a serotonin1A partial agonist, has been approved for treatment of generalized anxiety disorder (GAD), but it may also be useful in depression with subsyndromal anxiety symptoms or as an adjunctive treatment for depression.^16,17 Generally well tolerated, the most commonly reported adverse effects include dizziness, head- ache, nervousness, nausea, and restlessness. One disadvantage of buspirone(Drug information on buspirone) is the 2- to 4-week lag before improvement.

Antipsychotics. Although typical antipsychotics, such as haloperidol(Drug information on haloperidol), pimozide(Drug information on pimozide), and loxa­pine, have shown a degree of efficacy as adjunctive agents in the treatment of depression and anxiety, the burden of adverse effects and possible propensity to worsen depression have limited their use.¹⁸ Atypical antipsychotics (including olanzapine, risperidone, quetiapine, aripiprazole(Drug information on aripiprazole), and zi­prasidone) have been increasingly used to treat depressive and anxiety disorders, mostly as adjunctive agents in patients with refractory symptoms.¹⁹ Evidence for the use of atypical antipsychotics as monotherapy in unipolar depression is limited, with the exception of quetiapine(Drug information on quetiapine), which has recently had positive outcomes in both unipolar and bipolar depression, and has shown benefits for depression with comorbid anxiety disorders.^20,21

Benzodiazepines. These agents are helpful in anxiety disorders because of their rapid onset of action and generally good adverse-effect profile, which result in high patient acceptance and adherence; however, as with all psychotropics, the benefit to risk ratio must be considered (Table 3).²² However, common adverse effects include sedation, cognitive impairment, development of tolerance and dependence, and rebound anxiety on discontinuation. The risk of dependency, in particular, has led to cautious use of these agents, which are generally recommended for short-term use.

While there is some evidence that benzodiazepine monotherapy may improve milder forms of depression, such treatment is unlikely to benefit patients with severe melancholic forms and, in some patients, may worsen depression.^23,24 Nevertheless, when used as an adjunct to antidepressants for depression with comorbid anxiety disorders, benzodiazepines may have several benefits. They may diminish the initial worsening of agitation and anxiety seen in the early phases of antidepressant treatment (thereby improving adherence), and they may also produce more rapid improvement of both anxiety and depressive symptoms than antidepressants alone.²⁵

Anticonvulsants. Several anticonvulsants have been evaluated for their efficacy as monotherapy or adjunctive treatment in individual depressive and anxiety disorders but not in depression with comorbid anxiety disorders. Currently, the greatest evidence exists for valproate(Drug information on valproate) and lamotrigine(Drug information on lamotrigine), but specifically for bipolar depression, although there is early evidence of their benefit for panic disorder (PD), SAD, and PTSD.^26,27 In contrast, gabapentin(Drug information on gabapentin), pregabalin(Drug information on pregabalin), and topiramate(Drug information on topiramate) were found to help with these same anxiety disorders but were not shown to be effective as monotherapy for depression.²⁷

More recent preliminary findings indicate some benefits from pregabalin and tiagabine(Drug information on tiagabine) in GAD, with tiagabine monotherapy showing efficacy in major depressive disorder with anxious features.^25,28