Benzodiazepines for anxious depression

These findings emphasize the need to pay more attention to anxiety in depressed patients (especially those newly diagnosed) and for forceful treatment of anxious depression. Importantly, in the STAR*D study,¹¹ remission in anxious Level 1 (treated with citalopram) depressed patients was significantly less likely and took longer to occur than in patients with nonanxious depression. In addition, ratings of adverse effects frequency, intensity, and burden, as well as the number of serious adverse events, were significantly greater in the anxious depression group. Similarly, in Level 2 (either switched to bupropion, sertraline or venlafaxine, or citalopram augmented with bupropion or buspirone), patients with anxious depression fared significantly worse in both the switching and augmentation options. One wonders if Level 1 patients treated with benzodiazepines, and Level 2 patients switched to benzodiazepines or offered augmentation with them would not have fared better, especially in view of the fact that many old and new antidepressants have significant adverse effects and are difficult to discontinue due to withdrawal symptoms such as dizziness, vertigo, and, in case of newer antidepressants, brain “zaps.” Benzodiazepines certainly have serious withdrawal symptoms, including anxiety, rebound insomnia, and withdrawal seizures, especially when discontinued abruptly and when the dose was high. Thus, as is the case for many other medications (eg, steroids, anticoagulants, and some antidepressants), benzodiazepines must be tapered carefully in order to avoid discontinuance signs and symptoms. Because benzodiazepines have been involved in nearly one-third of overdose-related deaths (either separately or in combination with opioids), and the FDA strongly warns against co-prescribing benzodiazepines and opioids, they need to be prescribed appropriately, carefully weighing their risks and benefits.¹²

Because the analysis by Benasi et al⁶ demonstrated that benzodiazepines seem comparably effective as antidepressants in anxious depression, we should be considering using benzodiazepines as monotherapy for this indication more frequently and vigorously, considering their similar efficacy, faster onset of action, and better tolerability, while also considering their risks. Clinicians use them in combinations anyway. We also need rigorous trials comparing benzodiazepines with newer antidepressants for anxious depression.