Benzodiazepines vs Antidepressants for Anxiety Disorders

Offidani and colleagues1 gathered data through 2012 on published, controlled, and direct comparisons between benzodiazepines and antidepressants for anxiety disorders but were hindered, they said, by a “paucity of studies.” Their review encompassed 22 studies, 18 of which compared TCAs, such as amitriptyline, clomipramine, or imipramine, with benzodiazepines. Of the remaining studies, 3 compared SSRIs or SNRIs with benzodiazepines and 1 compared the MAOI phenelzine with benzodiazepines. Eleven studies in the meta-analysis compared a ben-zodiazepine with a TCA for the treatment of panic disorder with or without agoraphobia. While there has been a shift in recent years toward using such newer antidepressants as SSRIs and SNRIs as first-line treatments for anxiety disorders instead of benzodiazepines, Giovanni Andrea Fava, MD, Clinical Professor of Psychiatry at the State University of New York at Buffalo and one of the review’s coauthors, questioned whether the shift is warranted. “There is no evidence to suggest that antidepressant drugs are more effective than benzodiazepines in anxiety disorders,” he said. “Certainly, benzodiazepines have fewer side effects.” In their review, the authors cited results for various anxiety disorders. “In mixed anxiety, GAD [generalized anxiety disorder], and social phobia, a superior efficacy of TCAs did not clearly emerge,” they said. They acknowledged that studies “with mixed anxiety were difficult to evaluate because of the heterogeneous features of the samples and the confounding effects of depressive symptoms.” The meta-analysis of treatments for panic disorder showed “less efficacy” and tolerability of TCAs than benzodiazepines, according to the review authors. In trials that compared benzodiazepines with the newer antidepressants, the benzodiazepines “resulted in comparable or greater improvements and fewer adverse events in patients suffering from GAD or panic disorder,” Offidani and colleagues added. Hackett and colleagues2 compared diazepam and venlafaxine extended-release in 540 patients with GAD. Results showed no significant differences in response rates between groups, but discontinuations and adverse effects were more frequent in patients treated with venlafaxine. Feltner and colleagues3 compared lorazepam, paroxetine, and placebo for treatment of patients with GAD. “Both active treatments were effective in reducing anxiety-related psychiatric symptoms, while somatic features improved significantly only in patients taking lorazepam.” Nardi and colleagues4 conducted a randomized, open-label, naturalistic 8-week study to compare the efficacy and safety of treatment with clonazepam and paroxetine in patients with panic disorder with or without agoraphobia. Clonazepam resulted in fewer weekly panic attacks at week 4 and greater clinical improvements at week 8. Anxiety severity was significantly reduced with clonazepam at weeks 1 and 2, with no difference in panic disorder severity. Patients treated with clonazepam had fewer adverse events than patients treated with paroxetine. The most common adverse effects were drowsiness/fatigue (57%), memory/concentration difficulties (24%), and sexual dysfunction (11%) in the clonazepam group and drowsiness/fatigue (81%), sexual dysfunction (70%), and nausea/vomiting (61%) in the paroxetine group. Offidani and colleagues also cited a long-term follow-up study by Nardi and colleagues5 that compared the efficacy and safety of clonazepam and paroxetine over 3 years of treatment. Long-term treatment with clonazepam led to a small but significantly better Clinical Global Impression of Improvement rating than treatment with paroxetine. Both treatments similarly reduced the number of panic attacks and severity of anxiety. Patients treated with clonazepam had