Generalized anxiety disorder efficacy

Sramek, J.J., Tansman, M., Suri, A., Hornig-Rohan, M., Amsterdam, J.D., Stahl, S.M., Weisler, R.H. and Cutler, N. R. (1996) Efficacy of buspirone in generalized anxiety disorder with coexisting mild depressive symptoms. Journal of Clinical Psychopharmacology, 57, 287-291. 

Delle Chiaie, R., Pancheri, P., Casacchia, M., Stratta, P., Kotzalidis, G.D. and Zibellini, M. (1995) Assessment of the efficacy of buspirone in patients affected by generalized anxiety disorder, shifting to buspirone from prior treatment with lorazepam a placebo-controlled, doubleblind study. Journal of Clinical Psychopharmacology, 15,... 

Although promising in preclinical models of anxiety, the 5-HT3 receptor antagonist ondansetron has limited efficacy in panic disorder (Schneier et al. 1996) however, at higher doses (1 mg), ondansetron was superior to placebo in a study of patients with generalized anxiety disorder (Freeman et al. 1997). 

Dunn R, Reed TA, Copeland PD, Frye CA (1998) The nitric oxide synthase inhibitor 7-nitroindazole displays enhanced anxiolytic efficacy without tolerance in rats following subchronic administration. Neuropharmacology 37 899-904 Freeman AR, Westphal J, Norris G, Roggero B, Webb P, Freeman K (1997) Efficacy of ondansetron in the treatment of generalized anxiety disorder. Depress Anxiety 5 140-141... 

Rickels K, Pollack M, Lydiard R (2002) Efficacy and satety of pregabalin and alprazolam in generalized anxiety disorder. American Psychiatric Association Annual Meeting, vol. NR 162. American Psychiatric Press, Philadelphia Romeo E, A Strohle, F di Michele, G Spaletta, B Hermann, F Holsboer, A Pasini, R Rupprecht... 

Several preliminary lines of research have started to suggest that antidepressants, once considered ineffective in generalized anxiety disorder, may be very efficacious [Gorman and Kent 1999]. In particular, venlafaxine has been effective in treating generalized anxiety disorder in both open-label and double-blind trials, and imipramine and paroxetine were as effective as a benzodiazepine in the long-term treatment of generalized anxiety disorder. 

Ondansetron. The S-HTj antagonist ondansetron has been reported to be effective in the treatment of generalized anxiety disorder, with efficacy comparable to that of diazepam [Lader 1991). Sedation and rebound anxiety during withdrawal from ondansetron were not observed [Lader 1991). Ondansetron has been considered for phase 111 clinical trials for the treatment of social phobia and panic disorder. 

Suriclone. Suriclone is one of the most potent of all agents known to act at the benzodiazepine receptor. Its anxiolytic effects have been clearly demonstrated in rodents (Doble et al. 1992). It has also been demonstrated to be efficacious in the treatment of generalized anxiety disorder in humans (Ansseau et al. 1991). Animal work has shown it to have fewer side effects and less potential for interacting with alcohol than do benzodiazepines. These would represent significant advantages if they were also seen in humans. Repeated doses have failed to show tolerance and do not produce the change in set point of the GABAj receptor seen with the benzodiazepines. The reason for this is unclear but may be linked to a difference in the interaction of the cyclo-pyrrolones with the receptor compared with that of the benzodiazepines. 

Despite these rather discouraging efficacy data, it appears that a minority of patients do experience some improvement in OC symptoms with combined SRI-buspirone treatment [Pigott et al. 1992a). It is the clinical impression of one of the authors [W. K. G.) that buspirone addition may occasionally be helpful in reducing OC symptoms in OCD patients with comorbid generalized anxiety disorder. Controlled studies with sufficient numbers of OCD patients with comorbid generalized anxiety disorder would be required to test the validity of these observations. 

Lecrubier Y, Judge R Long-term evaluation of paroxetine, clomipramine and placebo in panic disorder. Acta Psychiatr Scand 95 153-160, 1997 Lecrubier Y, Puech AJ, Azcona A, et al A randomized double-blind placebo-con-trolled study of tropisetron in the treatment of outpatients with generalized anxiety disorder. Psychopharmacology 112 129, 1993 Lecrubier Y, Pletan Y, Selles A, et al Clinical efficacy of milnacipran placebo-con-trolled trials. Int Chn Psychopharmacol 11 (suppl 4 29-34, 1996 Lecrubier Y, Bakker A, Dunbar G, et al A comparison of paroxetine, clomipramine and placebo in the treatment of panic disorder. Acta Psychiatr Scand 95 145-152, 1997... 

Davidson JR, DuPont Rl, Hedges D, et al. Efficacy, safety and tolerability of venlafaxine extended release and buspirone in outpatients with generalized anxiety disorder. J Clin Psychiatry 1999 60 528-535. 

Rickels K, Pollack MH, Sheehan DV, et al. Efficacy of extended-release venlafaxine in nondepressed outpatients with generalized anxiety disorder. Am J Psychiatry 2000 157 968-974. 

Rocca P, Fonzo V, Scotta M, et al. Paroxetine efficacy in the treatment of generalized anxiety disorder. Acta Psychiatr Scand 1997 95 444-450. 

Lydiard RB, Ballenger JC, Rickels K. A double-blind evaluation of the safety and efficacy of abecarnil, alprazolam, and placebo in outpatients with generalized anxiety disorder. Abecarnil Work Group. J Clin Psychiatry 1997 58(suppl 11) 11-18. 

In addition to its efficacy as a first-line antidepressant, mirtazapine may have enhanced efficacy due to its dual mechanism of action (Fig. 7—3), especially in combination with other antidepressants that block serotonin and/or norepinephrine reuptake. This will be discussed below in the section on antidepressant combinations. Mirtazapine may also have utility in panic disorder, generalized anxiety disorder, and other anxiety disorders, but has not been intensively studied for these indications. 

SSRIs show efficacy in social phobia, and combined serotonin and norepinephrine uptake inhibitors are effective in generalized anxiety disorder. 

Fontaine R, Beaudry P, Le Morvan P, Beauclair L, Chouinard G (1990) Zopiclone and triazolam in insomnia associated with generalized anxiety disorder a placebo-controlled evaluation of efficacy and daytime anxiety. Int Clin Psychopharmacol 5 173-183... 

Escitalopram was efficacious in patients with major depressive disorder in short-term, placebo-controlled trials, three of which included citalopram as an active control, and in a 36-week study in the prevention of relapse in depression (7). It has also been used to treat generalized anxiety disorder, panic disorder, and social anxiety disorder. Results also suggest that, at comparable doses, escitalopram demonstrates clinically relevant and statistically significant superiority to placebo treatment earlier than citalopram. The most common adverse events associated with escitalopram include nausea, insomnia, disorders of ejaculation, diarrhea, dry mouth, and somnolence. Only nausea occurred in more than 10% of patients taking escitalopram. 

Alprazolam, a triazolobenzodiazepine, has been marketed as an anxiolytic with additional antidepressant properties an analogue, adinazolam, also has partial antidepressant activity (1) and is useful in panic disorder. Like other benzodiazepines, alprazolam is effective in acute and generalized anxiety its efficacy in panic disorder (2,3), premenstrual syndrome (4), and chronic pain (5) is complicated by high rates of adverse effects (6). On the other hand, low-dose alprazolam (1.4 mg/day) is useful and well tolerated in the treatment of anxiety associated with schizophrenia (SEDA-19, 34). 

In a multicenter, double-blind study, 310 patients with generalized anxiety disorder were treated for 6 weeks with abecarnil (mean daily dose 12 mg), diazepam (mean daily dose 22 mg), or placebo in divided doses for 6 weeks (11). Those who had improved at 6 weeks could volunteer to continue double-blind treatment for a total of 24 weeks. Slightly more patients who took diazepam (77%) and placebo (75%) completed the 6-week study than those who took abecarnil (66%). The major adverse events during abecarnil therapy were similar to those of diazepam, namely drowsiness, dizziness, fatigue, and difficulty in coordination. Abecarnil and diazepam both produced statistically significantly more symptom relief than placebo at 1 week, but at 6 weeks only diazepam was superior to placebo. In contrast to diazepam, abecarnil did not cause withdrawal symptoms. The absence of a placebo control makes it difficult to interpret the results of another study of the use of abecarnil and diazepam in alcohol withdrawal, which appeared to show comparable efficacy and adverse effects of the two drugs (12). 

A 6-week, double-blind, randomized, parallel, phase II, single-center, outpatient study has been performed to study the efficacy and safety of lesopitron 40-80 mg/day compared with lorazepam 2-4 mg/day and placebo in 161 patients with generalized anxiety disorder (1). The most common adverse events associated with lesopitron were somnolence, headache, and dyspepsia, compared with headache, somnolence, and insomnia with lorazepam. Patients treated with placebo mainly experienced headache, somnolence, and pharyngitis. 

Fresquet A, Sust M, Lloret A, Murphy MF, Carter FJ, Campbell GM, Marion-Landais G. Efficacy and safety of lesopitron in outpatients with generalized anxiety disorder. Ann Pharmacother 2000 34(2) 147-53. 

Llorca P, Spadone C, Sol O, et al. Efficacy and safety of hydroxyzine in the treatment of generalized anxiety disorder A 3-month double-blind study. J Clin Psychiatry 2002 63 1020-1027. 

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