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Benzodiazepines vs Antidepressants for Anxiety Disord

Published on Psychiatric Times

Benzodiazepines vs Antidepressants for Anxiety Disorders
News [1] | December 18, 2013 | Anxiety [2], Psychopharmacology [3]
By Arline Kaplan [4]
A recent systematic review and meta-analysis that compared benzodiazepines with antidepressants
for anxiety disorders has triggered a debate among clinicians about first-line treatments, efficacy for
specific disorders, and adverse effects.

A recent systematic review and meta-analysis that compared benzodiazepines with antidepressants
for anxiety disorders has triggered a debate among clinicians about first-line treatments, efficacy for
specific disorders, and adverse effects.
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
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It introduces more logistic complications to put them on a benzodiazepine and then to take them off of it six or eight weeks later. He uses benzodiazepines as “second-line” treatments for patients with anxiety disorders. “I don’t think anybody anymore realistically thinks benzodiazepines should be used as first-line [pharmacological] significantly fewer adverse events than those treated with paroxetine (28. The use of antipsychotics for anxiety disorders follows the same lines.Benzodiazepines vs Antidepressants for Anxiety Disord Published on Psychiatric Times (http://www.” He told Psychiatric Times. in terms of both efficacy and safety. criticized the study by Offi-dani and colleagues as being of limited value for informing clinical practice today.psychiatrictimes. such as personality disorder or a subacute alcohol problem.” In an editorial citing the systematic review. because GAD is a difficult diagnosis to make and is often comorbid with other disorders. there is also a withdrawal syndrome with antidepressants.” he said. who is also Professor of Clinical Psychology at the University of Bologna in Italy. of a reduced response to CBT. called for more comparison studies and contended that “no evidence for the superiority of the newer antidepressants over benzodiazepines. He also questioned the practice of using benzodiazepines to help reduce anxiety during the initial weeks of treatment with antidepressants when anxiolytic effects have yet to occur.” The most common use of benzodiazepines. . but continues them for the long term only if he sees substantial clinical improvement.” He said that it is better to use benzodiazepines for panic disorder and social anxiety disorder. “because they are easier to diagnose and less likely to be confused with other disorders.” Other disadvantages include cognitive and psychomotor impairments.” Advantages and drawbacks Both Fava and Roy-Byrne were asked about the advantages and drawbacks of benzodiazepines for anxiety disorders. Offidani and colleagues concluded that the change in the prescribing pattern that favors newer antidepressants over benzodiazepines in the treatment of anxiety disorders “has occurred without supporting evidence. for the simple reason that it compares benzodiazepines with older antidepressants. “Benzodiazepines should be considered first-line pharmacological treatment for all anxiety disorders with the possible exception of obsessive-compulsive disorder. Professor of Psychiatry at the University of Washington and one of the contributors to the American Psychiatric Association’s Practice Guideline for the Treatment of Panic Disorder (2009). the advantages of benzodiazepines “are that they are extremely potent and work very well.” Fava. P < . “The shift from benzodiazepines to antidepressants is one of the most spectacular achievements of propaganda in psychiatry.” said Fava. is in combination with antidepressants for individuals who have had suboptimal responses to antidepressants. MD. First-line treatment? Fava and Roy-Byrne disagreed about using benzodiazepines as first-line treatment for anxiety disorders. “Most of the time it is not worthwhile to use them to just take the edge off symptomatic distress.” said Fava. According to Roy-Byrne.” The older antidepressants. exists for either short-term or long-term treatment. Mudd Professor of Behavior and Reproduction in Psychiatry. though very short-term use in recently traumatized patients is a sound practice.7 “In my experience.” Peter Roy-Byrne. he explained. Roy-Byrne said.6 founder of the Mood and Anxiety Disorders Section at the University of Pennsylvania and Stuart and Emily B. because psychotherapy is very effective. using low doses of antidepressants and being in contact with patients frequently enough to answer their questions and provide them reassurance is usually sufficient to help them get used to the antidepressant over time. Benzodiazepines tend to be anti-CBT Page 2 of 4 . “Benzodiazepines are fast-acting and very well-tolerated drugs with few side effects and interactions with other medications. Their drawbacks are cognitive effects and dependence. A disadvantage is that you can become physically dependent on them.” Roy-Byrne countered. and most importantly.001). MD. noting that behavioral treatment might be a better alternative. believes the shift to the newer antidepressants was for “purely commercial reasons. “I think it is a flawed study. so it is much easier to show some advantage for benzodiazepines in comparison studies. In addition. except in rare cases. On the basis of their systematic review and meta-analysis. “Using benzodiazepines for PTSD over the long term is also likely to produce more harm than good.9% vs 70. While he prescribes benzodiazepines for anxiety disorders in some of his patients. not yet conclusively demonstrated. the possibility. . Roy-Byrne said GAD is “the absolute worst anxiety disorder” for which to use benzodiazepines. adding that drugs generally should not be the first-line treatment for anxiety disorders. TCAs are now rarely used for anxiety disorders. . although to be fair. have a greater adverse effect burden than the newer ones. abuse potential. Karl Rickels.6%. H.

Early coadministration of clonazepam with sertraline for panic disorder. But if they take a potent anti-anxiety drug. notably the London-Toronto study [by Nardi and colleagues5]. Braz J Med Biol Res. Hackett D. 3.15:12-18. Psychother Psychosom. 2001.32:206]. Psychopharmacotherapy of panic disorder: 8-week randomized trial with clonazepam and paroxetine. Brouette T. neither for acute nor chronic treatment. CNS Neurosci Ther.32:120-126. Guidi J. when possible.58:681-686. Offidani E. Harness J. 2012. benzodiazepines do the exact opposite.” Rickels said. there is currently no published study comparing this strategy with switching the antidepressant. Should benzodiazepines be replaced by antidepressants in the treatment of anxiety disorders? Fact or fiction. use of benzodiazepines decreased the efficacy of CBT. Freire RC. With regard to the newer antidepressants for anxiety disorders.” References: 1. Haudiquet V. 2009.82:355-362. particularly in younger patients. Roy-Byrne said “they are well-tolerated and they work more slowly than benzodiazepines. In an editorial on whether benzodiazepines still have a role in treating patients with anxiety disorders. 2011. other than the sexual dysfunction associated with most of the agents. Eur Psychiatry. “Whereas CBT is very good for anxiety because it toughens you up. et al. Tomba treatments. Valença AM. Studies The most common reason for using benzodiazepines is to add them to antidepressants when treating anxiety disorders that have not optimally responded to an initial antidepressant. Almai A. for placebo-controlled augmentation studies after non-response. Brock J. conducted.18:182-187.” “I agree that in some investigations. Efficacy and tolerability of benzodiazepines versus antidepressants in anxiety disorders: a systematic review and meta-analysis. et al. Nardi AE.44:366-373. after unsuccessful treatment with a selective serotonin reuptake inhibitor or cognitive behavior therapy. Freire RC. 2. 2013. A method for controlling for a high placebo response rate in a comparison of venlafaxine XR and diazepam in the short-term treatment of patients with generalised anxiety disorder. Rickels K. improves your coping ability. Arch Gen Psychiatry. J Clin Psychopharmacol. Feltner DE. CBT requires some anxiety that individuals need to experience upon exposure to desensitize themselves over time. Clinical evaluation of the Daily Assessment of Symptoms-Anxiety (DAS-A): a new instrument to assess the onset of symptomatic improvement in generalized anxiety disorder. Page 3 of 4 . but it is probably true that benzodiazepines may sometimes interfere with CBT programs. for example. they just won’t be anxious.8-10 Furthermore. A randomized. 5. 7. et al. Fava GA. Mochcovitch MD.”11 Antidepressants also entail the risk of a switch into an undiagnosed bipolar course. Goddard AW. 2003. and for well-designed relapse prevention studies. parallel-group study for the long-term treatment of panic disorder with clonazepam or paroxetine [published correction appears in J Clin Psychopharmacol.” There aren’t many drawbacks with the antidepressants. “A well-conducted comparison trial of a benzodiazepine and a newer antidepressant simply does not exist. “There is a persisting need for placebo-controlled combination studies in acute treatment.82:351-352. 4.” said Fava. According to Roy-Byrne. Nardi AE. 2013. and lets you become more resilient to stress. 6. although a report of the study is in press. by non-industry sources. naturalistic. “It has not been extensively investigated. which may provide needed information in this debate.” he said. “long-term outcome studies of panic disorder treated by behavioral methods disclosed a detrimental effect of antidepressants and not benzodiazepines. Salinas E. The same effect is seen with antidepressants in panic disorder and social phobia. Fava and Rickels call for further comparison studies. Baldwin and Talat12 said. Psychother Psychosom. 2012.Benzodiazepines vs Antidepressants for Anxiety Disord Published on Psychiatric Times (http://www. so they don’t provide patients with a clear-cut signaling link between taking a pill and feeling an anti-anxiety affect. 8. Exposure therapy and sertraline in social phobia: 1-year follow-up of a randomised controlled trial. Should benzodiazepines still have a role in treating patients with anxiety disorders? Hum Psychopharmacol. Long-term outcome of panic disorder with agoraphobia treated by exposure. JAMA. [2] http://www. [3] http://www.psychiatrictimes. Fava GA. et al. Barlow DH. et al.284:2597].Benzodiazepines vs Antidepressants for Anxiety Disord Published on Psychiatric Times (http://www. 11. Hellstrøm K.162:776-787.psychiatrictimes. imipramine. 1993. 2003.psychiatrictimes. Gorman JM. Blomhoff S. Rafanelli C. Shear MK. 9. Basoglu Links: [1] http://www. 2012. Baldwin DS. Source URL: http://www.283:2529-2536. Haug TT. Grandi S. Talat B. Br J Psychiatry. Br J Psychiatry.182:312-318. or their combination for panic disorder: a randomized controlled trial [published corrections appear in JAMA.psychiatrictimes. Page 4 of 4 [4] http://www. 12.31:891-898.284:2450.27:237-238. 10.psychiatrictimes. 2001. Cognitive-behavioral therapy. Woods SW. A controlled study in London and Toronto. Alprazolam and exposure alone and combined in panic disorder with agoraphobia. Swinson RP. et al. Psychol Med. Marks IM.