Buspirone adverse effects

Kranzler HR, Del Boca F, Korner P, et ah Adverse effects limit the usefulness of flu-voxamine for the treatment of alcoholism.] Subst Abuse Treat 10 283-287, 1993 Kranzler HR, Burleson JA, Del Boca FK, et ah Buspirone treatment of anxious alcoholics a placebo-controlled trial. Arch Gen Psychiatry 31 720—731, 1994 Kranzler HR, Burleson JA, Korner P, et ah Placebo-controlled trial of fluoxetine as an adjunct to relapse prevention in alcoholics. Am] Psychiatry 152 391-397, 1995 Kranzler HR, Burleson JA, Brown J, et al Fluoxetine treatment seems to reduce the beneficial effects of cognitive-behavioral therapy in type B alcoholics. Alcohol Clin Exp Res 20 1534-1341, 1996... 

Buspirone (BuSpar) [Anxiolytic] WARNING Closely monitor for worsening depression or emergence of suicidality Uses Short-term relief of anxiety Action Antianxiety antagonizes CNS serotonin receptors Dose Initial 7.5 mg PO bid T by 5 mg q2-3d to effect usual 20-30 mg/d max 60 mg/d Contra w/ MAOI Caution [B, /-] Avoid w/ severe hepatic/renal insuff Disp Tabs SE Drowsiness, dizziness, HA, N, EPS, serotonin synd, hostility, depression Notes No abuse potential or physical/psychologic d endence Interactions T Effects W/ erythromycin, clarithromycin, itraconazole, ketoconazole, diltiazem, verapamil, grapefruit juice effects W/ carbamazepine, rifampin, phenytoin, dexamethasone, phenobarbital, fluoxetine EMS T Sedation w/ concurrent EtOH use grapefruit juice may T risk of adverse effects OD May cause dizziness, miosis, N/V symptomatic and supportive... 

There is no cross-tolerance of buspirone with benzodiazepines or other sedative medications. Withdrawal symptoms, occurring for example after stopping benzodiazepine use are influenced by buspirone only to a minor extend. Adverse effects include dizziness, light-headiness, agitation, headache, tinnitus and nausea but those reactions are generally mild. 

The most common adverse events associated with buspirone use include dizziness, headache, nausea, ner-vounsness, lightheadedness, and agitation. These adverse effects decrease over time. Buspirone does not cause seizures or abnormal involuntary movements or impair psychomotor performance. 

Munjack et al. [1991] conducted a pilot study of buspirone in the treatment of social phobia. Subjects meeting DSM-lll-R criteria for social phobia were entered into an 8-week, open-label trial. Buspirone was started at 5 mg twice a day and increased by 5 mg every 2-3 days to a maximum dosage of 60 mg/day, or until side effects prevented further dose escalation. Of the 17 subjects entered in this study, 11 completed it. The 6 dropouts resulted from lack of responsiveness, adverse effects, inability to attend appointments, and a loss to follow-up. At week 6, of the 11 subjects completing the trial, 5 reported a little and 6 endorsed moderate change in their symptomatology. At the end of week 8, two subjects reported a little, 5 noted moderate, and 4 endorsed marked improvement. Although the global measures demonstrated the above results, instruments used to measure the features specific to social phobia demonstrated mixed results. 

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. 

More recently, non-BZD anxiolytics, such as buspirone, and nonbarbiturate, non-BZD hypnotics, such as zolpidem and zaleplon, have been developed. The more recent anxiolytics and hypnotics offer equal efficacy, fewer serious adverse effects, and less risk of a fatal consequence due to accidental or intentional overdose. Unfortunately, these compounds have not entirely eliminated the hazards of tolerance, dependency, and withdrawal syndromes, although they do have a lower abuse potential than their predecessors. 

Two studies have indicated that the tricyclic antidepressant (TCA) imipramine may be as effective as BZDs in the treatment of GAD ( 58, 59). No studies longer than 8 weeks duration have been conducted, however, and imipramine s onset of anxiolytic action may be even slower than that of buspirone. Aithough adverse effects also may limit usefulness, its lack of dependence liability may make it an appropriate alternative in chronically anxious patients who also suffer from panic and depression. 

The experience of pregnancy itself is often anxiety provoking, and symptoms sufficient to warrant drug therapy are common in this group ( 16). Although this discussion primarily focuses on the benzodiazepines (BZDs), antidepressants and buspirone may also be used for women of childbearing age with certain anxiety-related disorders. Perhaps the best-documented adverse effect of the BZDs is a neonatal withdrawal syndrome, which has been reported to occur with several of the agents (e.g., diazepam, alprazolam, and triazolam). In addition, there is a weak positive relationship between diazepam exposure and oral clefts ( 17). 

Beta-adrenoceptor antagonists, particularly propranolol, have been shown to be effective for anxiety symptoms particularly in situational anxiety and GAD. Buspirone, an azaspirodecanedione, is an agonist at 5-HTlA receptors and seems to have anxiolytic effects, though it is less potent than the BDZs and the effects take up to three weeks to become evident. There is high first pass metabolism and a considerable proportion of the effect is due to a metabolite (1-PP). The principal adverse effects of buspirone are nausea, gastrointestinal upset and headache. Antidepressant drugs, both the older tricyclic antidepressants and the newer drugs, have been demonstrated to have anxiolytic effects in mixed anxiety-depressive patients, GAD and panic disorder. 

Comparison of common adverse effects of buspirone and alprazolam. Results are expressed as percent of patients showing each symptom. 

A 49-year-old man had major adverse effects 11 days after taking a combination of sertraline, buspirone, and loxapine (25). The adverse effects were characteristic of the serotonin syndrome, which is characterized by a constellation of symptoms, including hypomania, agitation, seizures, confusion, restlessness, hyper-reflexia, tremor, myoclonus, ataxia, incoordination, anxiety, double vision, fever, shivering, variable effects on blood pressure, nausea and vomiting, sweating, and diarrhea. 

The effects of hydroxyzine 50 mg/day, buspirone 20 mg/day, and placebo have been studied in 244 patients with generalized anxiety disorder in a double-bhnd placebo-controlled study (16). Hydroxyzine (n = 81) was considerably better than placebo (n = 81), and buspirone (n = 82) was intermediate. The main adverse effects were headache and migraine with buspirone (6.1 versus 4.9% with hydroxyzine and 1.2% with placebo). Somnolence occurred in 9.9% with hydroxyzine, 4.9% with buspirone, and none with placebo. Dizziness occurred in 6.1% with buspirone, none with hydroxyzine, and 2.5% with placebo. 

The efficacy and safety of buspirone have been evaluated in the management of anxiety and irritability in 22 children with pervasive developmental disorders. One child developed abnormal involuntary movements of the mouth, cheeks, and tongue after having taken buspirone 20 mg/day for 10 months. No other drugs were prescribed. The abnormal movements disappeared completely within 2 weeks of withdrawal of buspirone. Other adverse effects... 

In a randomized placebo-controlled trial, the possible interactions of buspirone with verapamil and diltiazem were investigated. Both verapamil and diltiazem considerably increased plasma buspirone concentrations, probably by inhibiting CYP3A4. Thus, enhanced effects and adverse effects of buspirone are possible when it is used with verapamil, diltiazem, or other inhibitors of CYP3A4 (24). 

Omeprazole, like cimetidine, can impair benzodiazepine metabolism and lead to adverse effects (SEDA-18, 43). Other drugs, including antibiotics (erythromycin, chloramphenicol, isoniazid), antifungal drugs (ketoconazole, itraconazole, and analogues), some SSRIs (fluoxetine, paroxetine), other antidepressants (nefazodone), protease inhibitors (saquinavir), opioids (fentanyl), calcium channel blockers (diltiazem, verapamil), and disulfiram also compete for hepatic oxidative pathways that metabolize most benzodiazepines, as well as zolpidem, zopiclone, and buspirone (SEDA-22,39) (SEDA-22,41). 

BZs should be reserved for patients at low risk of substance abuse, those who require rapid relief, or those who have not responded to other therapies. Clonazepam is the most extensively studied BZ for treatment of generalized SAD. It improved fear and phobic avoidance, interpersonal sensitivity, fears of negative evaluation, and disability measures. Adverse effects include sexual dysfunction, unsteadiness, dizziness, and poor concentration. Clonazepam should be tapered at a rate not to exceed 0.25 mg every 2 weeks. Gabapentin was effective for SAD, and onset of effect was 2 to 4 weeks. j8-Blockers blunt the peripheral autonomic symptoms of arousal (e.g., rapid heart rate, sweating, blushing, and tremor) and are often used to decrease anxiety in performance-related situations. For specific SAD, 10 to 80 mg of propranolol or 25 to 100 mg of atenolol can be taken 1 hour before the performance. A test dose should be taken at home on a day before the performance to be sure adverse effects wUl not be problematic. Incomplete response to a first-line agent may benefit from augmentation with buspirone or clonazepam. 

BZDs PROTEASE INHIBITORS t adverse effects, e.g. prolonged sedation Inhibition of CYP3A4-mediated metabolism of BZDs and buspirone Watch closely for t sedation 4 dose of sedative as necessaiy. Some recommend considering substituting long-acting for shorter-acting BZDs with less active metabolites (e.g. lorazepam for diazepam)... 

BUSPIRONE-ORAL GRAPEFRUIT JUICE Possibly t efficacy and t adverse effects, e.g. sedation, CNS depression Possibly t bioavailability, 1 presystemic metabolism. Constituents of grapefruit juice irreversibly inhibit intestinal CYP3A4. Transport via P-gp and MRP-2 efflux pumps is also inhibited Avoid concomitant use. Be particularly vigilant in elderly patients or those with impaired liver function. Consider an alternative, e.g. temazepam... 

In a 21-day, open, multicenter, dose-escalation study, 13 children and 12 adolescents with anxiety disorder and 14 healthy adults took buspirone 5-30 mg bd titrated over 3 weeks (17). Buspirone was generally safe and well-tolerated at doses up to 30 mg in adolescents and adults and in most of the children. The most common adverse events in children and adolescents were light-headedness (68%), headache (48%), and dyspepsia (20%) two children withdrew from the study at the higher doses (15 mg and 30 mg bd) owing to adverse effects. In adults, the most common adverse event was somnolence (21%) mild lightheadedness, nausea, and diarrhea were also reported. 

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