Buspirone generalized anxiety

Iwata N, Cowley DS, Radel M, et al Relationship between a GABA alpha g Pro385Ser substitution and benzodiazepine sensitivity. Am] Psychiatry 156 1447—1449,1999 Jacobson AF, Dominguez RA, Goldstein B, et al Comparison of buspirone and diazepam in generalized anxiety disorder. Pharmacotherapy 5 290—296, 1985 Jaffe JH, Ciraulo DA, Nies A, et al Abuse potential of halazepam and diazepam in patients recently treated for acute alcohol withdrawal. Clin Pharmacol Ther 34 623-630, 1983... 

Tollefson GD, Montague-Clouse J, Tollefson SL Treatment of comorbid generalized anxiety in a recently detoxified alcohol population with a selective serotonergic drug (buspirone). J Clin Psychopharmacol 12 19-26, 1992... 

Generalized anxiety Duloxetine Escitalopram Paroxetine Venlafaxine XR Benzodiazepines Buspirone Imipramine Sertraline Hydroxyzine Pregabalin... 

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,... 

Gammans, R.E., Stringfellow, J.C., Hvizdos, A.J., Seidehamel, R.J., Cohn, J. B., Wilcox, C.S., Fabre, L.F., Pecknold, J. C Smith, W.T. and Rickels, K. (1995) Use of buspirone in patients with generalized anxiety disorder and coexisting depressive symptoms. A meta-analysis of eight randomized, controlled studies. Neuropsychobiology, 25, 193-201. 

Buspirone. A nonbenzodiazepine anxiolytic, buspirone is an effective treatment for generalized anxiety disorder but not other anxiety disorders. There are as yet no published controlled studies of buspirone for PTSD, though a small open label series suggested it might be effective for the core symptoms of PTSD. In the absence of more definitive evidence regarding its effectiveness, we do not routinely use buspirone when treating PTSD. 

The full complement of anxiety syndromes including panic, generalized anxiety, obsessive-compulsiveness, and post-traumatic stress disorder can arise in the after-math of TBI. In fact, anxiety may be the most common neuropsychiatric complication of TBI. Anxiety appears to be most likely to arise when the injury occurs to the right side of the brain. The treatment alternatives for post-TBl anxiety parallel those used when treating anxiety disorders and include serotonin-boosting antidepressants, buspirone (Buspar), and the benzodiazepines (see Table 12.1). 

With regard to generalized anxiety disorder, it has been postulated that an overactivity of the stimulatory 5-HT pathways occurs. Drugs such as buspirone and ipsapirone are effective in such conditions because they stimulate the inhibitory S-HT a autoreceptors on the raphe nuclei and thereby reduce serotonergic function. It is noteworthy that the SSRIs often worsen anxiety initially because they temporarily enhance serotonergic function. Adaptive changes in the pre- and postsynaptic 5-HT receptors then occur leading to a reduction in the anxiety state. 

Enkelmann R (1991) Alprazolam versus buspirone in the treatment of outpatients with generalized anxiety disorder. Psychopharmacology (Berl) 105 428-432 Faravelli C, Rosi S, Truglia E (2003) Treatments benzodiazepines. In Nutt DJ, BaUenger JC (eds) Anxiety disorders. Blackwell Science, Oxford, pp 315-338 Fawcett J, Barkin RL (1998) A meta-analysis of eight randomized, double-blind, controlled clinical trials of mirtazapine for the treatment of patients with major depression and symptoms of anxiety. J Clin Psychiatry 59 123-127 Febbraro GA, Clum GA (1998) Meta-analytic investigation of the effectiveness of self-regulatory components in the treatment of adult problem behaviors. Clin Psychol Rev 18 143-161... 

LaderM,ScottoJC( 1998) A multi centre double-blind comparison of hydroxyzine, buspirone and placebo in patients with generalized anxiety disorder. Psychopharmacology (Berl) 139 402-406... 

Buspirone is as effective as the benzodiazepines in the treatment of general anxiety. However, the full anxiolytic effect of buspirone takes several weeks to develop, whereas the anxiolytic effect of the benzodiazepines is maximal after a few days of therapy. In therapeutic doses, buspirone has little or no sedative effect and lacks the muscle relaxant and anticonvulsant properties of the benzodiazepines. In addition, buspirone does not potentiate the central nervous system depression caused by sedative-hypnotic drugs or by alcohol, and it does not prevent the symptoms associated with benzodiazepine withdrawal. 

Buspirone is effective in general anxiety and in anxiety with depression. 

Buspirone has been shown to be very effective in treating generalized anxiety disorder (GAD). It is especially useful when combined with a benzodiazepine, probably because using these two drugs together causes the activation of two neurotransmitter systems (GABA and serotonin). 

Generalized anxiety disorder is still considered the gold standard indication for benzodiazepines (P. J. Perry et al. 1990]. However, buspirone, a serotonin-la partial agonist, has been demonstrated as effective in this disorder... 

Goa and Ward 1986 Pecknold et al. 1989 Rickels et al. 1982]. In contradistinction to benzodiazepines, the therapeutic effect of buspirone has a lag period similar to that of antidepressants in depression, suggesting that its therapeutic benefits derive from receptor modulation. In addition, buspirone seems to act preferentially in those patients who are not responsive to benzodiazepines, suggesting a possible subgrouping of generalized anxiety disorders. 

Feighner and Cohen [1989) performed a pooled-data analysis of six studies of buspirone in the treatment of generalized anxiety disorder. Buspirone was observed to improve all symptom groups on the Hamilton Anxiety Scale [M. Hamilton 1959). Onset of anxiolytic therapy was evident within 1 week, whereas continued improvement was evident until the 4-week end point. The psychic symptoms of anxiety, such as anxious mood, tension, irritability,... 

In summary, buspirone is an effective generalized anxiety treatment that differs from conventional antianxiety drugs in speed of symptom reduction and types of symptoms affected. Although buspirone might seem to be the drug of choice for treatment of chronic anxiety, it has not displaced the use of benzodiazepines in the treatment of anxiety, perhaps because of its side-effect profile [dizziness, sedation, nausea], slow onset of action, and the opinion of some clinicians that its anxiolytic efficacy is less robust than that of benzodiazepines. Buspirone is accepted as an anxiolytic treatment much more widely in the United States than in most other countries [Kunovac and Stahl 1995]. 

Preliminary phase II clinical data have shown that gepirone is an effective anxiolytic that significantly reduces both psychic and somatic symptoms of generalized anxiety disorder. Like buspirone, gepirone does not impair memory, verbal fluency, or psychomotor performance [Harto and Branconnier 1988]. 

Alpidem. Alpidem is an imidazopyridine partial agonist that also shows relative selectivity for the type I benzodiazepine receptor. Studies have shown an anxiolytic effect comparable with the classic benzodiazepines, but with an improved adverse effect profile [Pancheri et al. 1993). It has also been compared with buspirone in patients with generalized anxiety disorder and shown to be more rapidly effective and again to have a more favorable adverse effect profile [Legris et al. 1993). Longer-term studies with alpidem have shown that tolerance does not occur, and no significant problems of withdrawal on discontinuation were found [Chevalier et al. 1993). Alpidem was licensed in France for the treatment of anxiety but has now been suspended because of recent reports of alpidem-induced hepatic dysfunction. The reason for this is unclear, but it may be a reflection of the fact that alpidem also binds to peripheral benzodiazepine receptors, which are present in high density in the liver. 

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. 

Notwithstanding the clinical use of many 5-HTj, receptor ligands for the treatment of anxiety, only one report was found that has investigated the potential to influence cognitive performance. In patients with a generalized anxiety disorder, Lucki et al. [1987] compared the effect of buspirone [at 5 and 10 mg] with that of diazepam [5 mg]. Diazepam impaired performance buspirone was without effect. 

Richelson E, Nelson A Antagonism by neuroleptics of neurotransmitter receptors of normal brain in vitro. Eur J Pharmacol 103 197-204, 1984 Rickels K, Schweizer E The treatment of generalized anxiety disorder in patients with depressive symptomatology. J Clin Psychiatry 54 [suppl) 20-23, 1993 Rickels K, Weisman K, Norstad N, et al Buspirone and diazepam in anxiety a controlled study. J Chn Psychiatry 43(12 pt 2) 81-86, 1982 Rickels K, Feighner JP, Smith WT Alprazolam, amitriptyline, doxepin, and placebo in the treatment of depression. Arch Gen Psychiatry 42 134-141, 1985 Rickels K, Schweizer E, Weiss S, et al Maintenance drug treatment for panic disorder, 11 short- and long-term outcome after drug taper. Arch Gen Psychiatry 50 61-68, 1993... 

Generalized anxiety disorder Buspirone, benzodiazepines, venlafaxine, SSRIs... 

TABLE 12-3. Buspirone versus placebo ora benzodiazepine for generalized anxiety disorder... 

DeMartinis N, Ryan M, Rickels K, et al. Prior benzodiazepine use and buspirone response in the treatment of generalized anxiety disorder. J Clin Psychiatry 2000 61 91-94. 

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. 

Pollack MH, Worthington JJ, Manfro GG, et al. Abecarnil for the treatment of generalized anxiety disorder a placebo-controlled comparison of two dosage ranges of abecarnil and buspirone. J Clin Psychiatry 1997 58(suppl 11) 19-23. 

Buspirone has minimal abuse liability. In marked contrast to the benzodiazepines, the anxiolytic effects of buspirone may take more than a week to become established, making the drug unsuitable for management of acute anxiety states. The drug is used in generalized anxiety states but is less effective in panic disorders. 

Buspirone Mechanism uncertain Partial agonist at 5-HT receptors but affinity for D2 receptors also possible Slow onset (1-2 weeks) of anxiolytic effects t minimal psychomotor impairment—no additive CNS depression with sedative-hypnotic drugs Generalized anxiety states Oral activity forms active metabolite short half-life Toxicity Tachycardia paresthesias t gastrointestinal distress Interactions CYP3A4 inducers and inhibitors... 

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