Buspirone discontinuation

Buspirone is well-tolerated, with the main side-effects being dizziness, anxiety, nausea and headache. It is tolerated by the elderly (Bohm et al. 1990). It does not cause sexual dysfunction and does not appear to be associated with a discontinuation syndrome. Overdose causes drowsiness but there are no reports of serious toxic effects. A potential for interaction with drugs that inhibit the CYP450 3A4 isoenzyme is not a significant problem in cHnical practice. GAD is usually a chronic condition and buspirone is suitable for long-term treatment. Patients should be advised to expect a slow onset of benefits and be reviewed regularly in the early stages of treatment. 

Buspirone is not associated with any withdrawal syndrome. Little is known about discontinuing the dosage, but a conservative approach would include a brief taper. 

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. 

Anderson DN, Wilkinson AM, Abou-Saleh MT, et al Recovery from depression after electroconvulsive therapy is accompanied by evidence of increased tetra-hydrobiopterin-dependent hydroxylation. Acta Psychiatr Scand 90 10-13, 1994 Anderson IM, Cowen PJ Effect of pindolol on endocrine and temperature responses to buspirone in healthy volunteers. Psychopharmacology 106 428-432, 1992 Anderson IM, Tomenson BM Treatment discontinuation with selective serotonin reuptake inhibitors compared with tricyclic antidepressants a meta-analysis. BMJ 310 1433-1438, 1995... 

Patel J, Keith RA, Salama AI, et al Role of calcium in regulation of phosphoinositide signaling pathway. J Mol Neurosci 3 1-9, 1991 Patil VJ Development of transient obsessive-compulsive symptoms during treatment with clozapine. Am J Psychiatry 149 272, 1992 Pato MT, Zohar-Kadouch R, Zohar J, et al Return of symptoms after discontinuation of CMl in patients with OCD. Am J Psychiatry 145 1521-1522, 1988 Pato PT, Pigott TA, Hill JL, et al Controlled comparison of buspirone and CMl in OCD. Am J Psychiatry 148 127-129, 1991 Patterson JF Treatment of acute mania with verapamil (letter). J Clin Psycho-pharmacol 7 206-207, 1987... 

Other than slow taper, no consistently effective treatment to alleviate withdrawal symptoms has been reported. Although several compounds have been studied (e.g., b-blockers, clonidine, carbamazepine, abercamil, ondansetron), results have been contradictory ( 250). Carbamazepine, however, may be useful in seizure-prone patients (251). Valproate (VPA) has also been reported to benefit patients undergoing BZD discontinuation after long-term dependence ( 252), which may be related to VPA s potential anxiolytic properties, its ability to alleviate withdrawal phenomena, or both. The azaspirone anxiolytic buspirone has been reported ineffective in suppressing withdrawal symptoms, particularly in long-term BZD users (253, 254). Hydroxyzine has also been found beneficial in treating patients for lorazepam withdrawal (255). 

Occasional Confusion amnesia disinhibition paradoxical excitement depression dizziness witiidrawal symptoms, including convulsions, on abrupt discontinuance (witiidrawal may be especially difficult with alprazolam) rebound insomnia or excitement Rare Hypotension blood dyscrasias jaundice allergic reactions paradoxical rage reactions stuttering with alprazolam BUPROPION, Anxiety agitation insomnia tremor anorexia BUSPIRONE, Dizziness headache nausea paresthesias diarrhea CHLORDIAZEPOXIDE, see Benzodiazepines CHLORPROMAZINE, see Phenothiazines, aliphatic CHLORPROTHIXENE, similar to Phenothiazines CLOMIPRAMINE, see Tricyclic antidepressants CLORAZEPATE, see Benzodiazepines CLOZAPINE... 

The side effects are similar too, but less severe than the 5-HT reuptake-inhibitors (for review see [2]). A sustained release formulation of buspirone is in Phase III clinical trial. The development of gepirone for the indication depression is discontinued. Tandospirone is awaiting registration for the indication depressive neurosis in Japan [3]. Ipsapirone and flesinoxan are in Phase III clinical trial. 

Buspirone is available as the hydrochloride salt (5 and 10 mg tablets) and is often considered to be useful for generalised anxiety disorder (GAD). Anxiolysis does not coincide with benzodiazepine-like sedation. The remaining derivatives are currently not available in most countries although tandospirone appears to he approved in Japan. The development of ipsapirone has heen discontinued and approval for gepirone for the treatment in depression is still being sought. 

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