Buspirone side effects

The anxiolytic agent buspirone (131) is notable for the fact that it does not interact with the receptor for the benzodiazepines. This difference in biochemical pharmacology is reflected in the fact that buspirone (131) seems to be devoid of some of the characteristic benzodiazepine side effects. The spiran function is apparently not required for anxiolytic activity. Alkylation of 3,3-dimethylglutarimide with dichlorobutane in the presence of strong base yields the intermedi-... 

Anxiolytics are drugs used for the treatment of anxiety disorders. Apart from benzodiazpines, a frequently used anxiolytic is the 5HT1A (serotonin) receptor agonist buspiron, which has no sedative, amnestic or muscle-relaxant side effects, but whose action takes about a week to develop. Furthermore, it is less efficaceous than the benzodiazepines. Buspiron s mechanism of action is not fully understood. 

Anxiolytics with little abuse potential, such as buspirone, and antidepressants that have a benign side-effect profile and may reduce ethanol intake warrant careful evaluation in the treatment of anxious and depressed alcoholic patients. 

Importantly, they achieve this without inducing extrapyramidal side-effects or increasing prolactin secretion, which are real problems with neuroleptics. These results have been borne out by preliminary clinical trials of buspirone, used in combination with neuroleptics, and several novel S-HTja agonists (e.g. BSF 190555) are currently under development for this clinical application (Meltzer 1999). 

Buspirone generally is well tolerated and does not cause sedation. Most common side effects include dizziness, nausea, and headaches. Drugs that inhibit CYP3A4 (e.g., verapamil, diltiazem, itraconazole, fluvoxamine, nefa-zodone, and erythromycin) can increase buspirone levels. Likewise, enzyme inducers such as rifampin can reduce buspirone levels significantly. Bupirone may increase blood pressure when coadministered with an monoamine oxidase inhibitor (MAOI). 

To overcome these side effects, buspirone has to be gradually titrated for several days or weeks until it reaches the therapeutic dose, taking weeks for the drug to be effective and not always reaching a fully effective dose. Its short half-life in humans necessitates three-times a day (tid) dosage, which also makes it less attractive compared to the once a day dosage of SSRIs. 

Buspirone (Buspar). Buspirone is an anxiety-relieving medication that alters serotonin activity. When added to an antidepressant, buspirone may help treat the depression. It will also relieve anxiety and may reverse sexual side effects of a SSRl. Please refer to Chapter 5 Anxiety Disorders for more information regarding buspirone. 

Buspirone does not share any of the problematic benzodiazepine properties such as sedation, motor impairment, addiction, physical dependence, or withdrawal. The most common side effects of buspirone include dizziness, nausea, headache, fatigue, and dry mouth. Despite its activity in the serotonin system, buspirone is not associated with the sexual side effects that plague the SSRIs, SNRIs, MAOIs, and TCAs. 

The subset of patients with GAD who do not have a comorbid depressive illness can be treated with buspirone in lieu of an antidepressant. Like the antidepressants, the buspirone treatment response is delayed by several weeks however, opting for buspirone is less likely to cause the transient exacerbation of anxiety or the sexual side effects commonly witnessed with antidepressants. Unfortunately, the usefulness of buspirone is severely limited by its requirement that it be administered two to... 

Buspirone (Buspar). Buspirone is a nonbenzodiazepine anxiety-reducing medication. It can be an effective treatment for demented patients with chronic anxiety. Buspirone is not sedating like the benzodiazepines and in fact probably has the fewest side effects of any available psychiatric medication. Buspirone does have a delayed onset of action therefore, it is not useful for acute treatment of anxiety or agitation. 

As noted in the previous section, buspirone produces both serotonin-boosting and serotonin-blocking effects by stimulating the serotonin-lA receptor. These mixed effects produce an overall milder serotonin-boosting effect that limits it potential side effects but also results in a more limited range of clinical uses than is available to other serotonin-boosting medications. Clearly, we cannot really say that buspirone blocks serotonin activity in the same way that antipsychotics block dopamine activity. 

Buspirone is an extremely specific drug that could possibly represent a new chemical class of anxiolytics—azaspirones. As an anxiolytic, its activity is equal to that of benzodiazepines however, it is devoid of anticonvulsant and muscle relaxant properties, which are characteristic of benzodiazepines. It does not cause dependence or addiction. The mechanism of its action is not conclusively known. It does not act on the GABA receptors, which occurs in benzodiazepine use however, it has a high affinity for seratonin (5-HT) receptors and a moderate affinity for dopamine (D2) receptors. Buspirone is effective as an anxiolytic. A few side effects of buspirone include dizziness, drowsiness, headaches, nervousness, fatigue, and weakness. This drug is intended for treatment of conditions of anxiety in which stress, muscle pain, rapid heart rate, dizziness, fear, etc. are observed in other words, conditions of anxiety not associated with somewhat common, usual, and everyday stress. Synonyms for buspirone are anizal, axoren, buspar, buspimen, buspinol, narol, travin, and others. 

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. 

Like the benzodiazepines, buspirone appears to be safe even when given in very high doses. The most common side effects are dizziness, light-headedness, and headache. Abuse, dependence, and withdrawal have not been reported, and buspirone administration does not produce any cross-tolerance to the benzodiazepines. Buspirone has been reported to increase blood pressure in patients taking monoamine oxidase inhibitors, and it may increase plasma levels of haloperidol if coadministered with that agent. 

Buspirone has very few side effects, which is another reason it is widely prescribed. 

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]. 

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. 

The use of buspirone in social phobia has also been investigated by Schneier et al. [1993]. In this 12-week open trial, 21 patients who met DSM-III-R criteria for social phobia and did not display a response during a 1 -week placebo run-in, went on to receive buspirone. The drug was initiated at 5 mg three times a day and was increased by 5 mg/day every 3 days to a maximum dosage of 60 mg/day or until side effects prevented further dose increases. Seventeen patients completed the trial. At the end of week 12, 8 [47%] of the 17 subjects were rated as much to very much improved on the Clinical Global Impression Scale (Guy 1976]. Of those subjects tolerating doses of 45 mg/day or more, 67% [9/12] were at least much improved. ... 

The side effects that are more common with buspirone therapy than with benzodiazepine therapy are nausea, headache, nervousness, insomnia, dizziness, and hght-headedness. Restlessness also has been reported. 

Treatment of GAD can be undertaken using a number of pharmacological agents. Benzodiazepines have been found to be superior to placebo in several studies and all benzodiazepines appear to be equally effective. However, side effects include sedation, psvchomotor impairment, amnesia and tolerance (Chapter 1). Recent clinical data indicate that SSRIs and SNRIs are effective in the treatment of acute GAD symptoms. Venlafaxine, paroxetine and imipramine have been shown to be effective antianxiety medications in placebo-controlled studies. Case studies also indicate the usefulness of clomipramine, nefazodone, mirtazapine, fluoxetine and fluvoxamine in GAD. Buspirone, a 5-HTla receptor partial agonist, has been shown to be effective in several placebo-controlled, double-blind trials (Roy-Byme and Cowley, 2002). Buspirone has a later onset of action than both benzodiazepines and SSRIs but with the advantage of being non-addictive and non-sedating. 

The side-effect profile of buspirone is different from BZDs in that there is ... 

Buspirone may be an effective anxiolytic in the elderly patient and less likely than BZDs to produce excessive sedation ( 352, 353, 354 and 355). Dizziness, however, may be a problem. Zolpidem or zaleplon, particularly in lower doses (i.e., 2.5 to 5.0 mg at bedtime) may be viable alternatives ( 356). The elimination half-life of these two agents is approximately 3 hours in the elderly. Although it has sleep-enhancing properties similar to BZD hypnotics, it is less likely to alter sleep architecture. Whereas antidepressants and b -blockers may be useful alternatives in younger patients, no data document their effectiveness for anxiety in elderly patients ( 307). Although antipsychotics may be helpful in reducing severe agitation, their side effect profile makes them unsuitable for use in subjective anxiety states ( 300, 307). 

FIGURE 8—11. Serotonin 1A partial agonists such as buspirone may reduce anxiety by actions both at presynaptic somatodendritic autoreceptors (left) and at postsynaptic receptors (right). Presynaptic actions are more likely related to anxiolytic actions, and postsynaptic actions are perhaps more likely linked to side effects such as nausea and dizziness. 

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