Buspirone observational studies

Anxiety disorders are common in the population of opioid-addicted individuals however, treatment studies are lacking. It is uncertain whether the frequency of anxiety disorders contributes to high rates of illicit use of benzodiazepines, which is common in methadone maintenance programs (Ross and Darke 2000). Increased toxicity has been observed when benzodiazepines are co-administered with some opioids (Borron et al. 2002 Caplehorn and Drummer 2002). Although there is an interesting report of clonazepam maintenance treatment for methadone maintenance patients who abuse benzodiazepines, further studies are needed (Bleich et al. 2002). Unfortunately, buspirone, which has low abuse liability, was not effective in an anxiety treatment study in opioid-dependent subjects (McRae et al. 2004). Current clinical practice is to prescribe SSRIs or other antidepressants that have antianxiety actions for these patients. Carefully controlled benzodiazepine prescribing is advocated by some practitioners. 

These observations question the role of noradrenaline as an initiator of anxiety as does the finding that the anti-anxiety drug, buspirone (see Chapter 9), increases the concentration of noradrenaline in the extracellular fluid in the frontal cortex of freely-moving rats (Done and Sharp 1994). Whether this is because buspirone is metabolised to l-(2-pyrimidinyl)-piperazine (1-PP), which is an a2-adrenoceptor antagonist, is uncertain. Unfortunately, no studies have investigated the effects of chronic administration of this drug on noradrenergic transmission this could be important because, unlike benzodiazepines, buspirone is effective therapeutically only after several weeks of treatment. 

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,... 

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. 

Other studies revealed that 5-HTj full flesinoxan and partial agonists [29], buspirone [30] and ipsapirone [31] also facilitated male sexual behaviour in rats. By contrast, male mice showed no facilitation of male sexual behaviour, but rather an inhibition [32]. In ferrets, 8-OH-DPAT, similarly inhibited masculine sexual behaviour [33]. In rhesus monkeys, however, facilitatoiy effects on male sexual behaviour were observed, albeit in more limited dose range for 8-OH-DPAT than for ipsapirone [34]. 

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