Buspirone dosing

Buspirone doses can be titrated in increments of 5 mg/day every 2 or 3 days as needed. 

Via CYP450 3A4, nefazodone may increase plasma concentrations of buspirone, so buspirone dose may need to be reduced... 

Ciraulo DA, Sands BE, Shader RI Critical review of liability for benzodiazepine abuse among alcoholics. Am J Psychiatry 145 1501-1506, 1988b Ciraulo DA, Barnhill JG, Ciraulo AM, et al Parental alcoholism as a risk factor in benzodiazepine abuse a pilot smdy. Am J Psychiatry 146 1333-1335, 1989 Ciraulo DA, Antal EJ, Smith RB, et al The relationship of alprazolam dose to steady-state plasma concentrations. J Clin Psychopharmacol 10 27—32, 1990 Ciraulo DA, Sarid-Segal O, Knapp C, et al Liability to alprazolam abuse in daughters of alcoholics. Am J Psychiatry 153 956-958, 1996 Ciraulo DA, Barnhill JG, Ciraulo AM, et al Alterations in pharmacodynamics of anxiolytics in abstinent alcoholic men subjective responses, abuse liability, and electroencephalographic effects of alprazolam, diazepam, and buspirone. J Clin Pharmacol 37 64-73, 1997... 

We have not explored all of the dose-response relationships. And with respect to the nature of the cue, we have studies underway now with a variety of serotonin agonists and antagonists, for example, fluoxetine. And have looked at MDMA. We eannot bloek the cue with fluoxetine. We are also looking at 8-hydroxy-DPAT, buspirone. PCPA pretreatment is on the way. So there are a variety of manipulations that we have in process. 

Buspirone should be initiated at a dose of 7.5 mg twice daily and titrated in 5 mg/day increments (every 2-3 days) to a usual target dose of 20 to 30 mg/day.41 The maximum daily dose is considered to be 60 mg/day. 

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. 

There are two principal disadvantages of buspirone therapy. First, it must be administered two or three times daily. Long-term patient compliance is notoriously poor for medications that cannot be administered in a single daily dose. Second, buspirone is not an effective treatment for depression or any of the other comorbidities that frequently accompany GAD. As a result, buspirone monotherapy is only an alternative for GAD patients who have no comorbid illness. 

The typical starting dose for buspirone is 15-20mg/day, administered either as a regimen of 5 mg taken three times each day or 10 mg taken twice daily. The efficacy of buspirone is typically maximized at a daily dose of 30-60 mg. The maximal daily dose of 60 mg can be administered either as 20 mg taken three times daily or 30 mg taken twice daily. 

We do not use benzodiazepines as readily when treating GAD as we do when treating panic disorder. In comparison to those with panic disorder, most patients with GAD can more easily tolerate the delay in treatment response and even any transient exacerbation of anxiety associated with antidepressant therapy. Benzodiazepines are reserved for those who present with especially severe anxiety that necessitates more rapid relief than an antidepressant can afford and for those who do not achieve a satisfactory response to antidepressant or buspirone therapy. Due to the persistent nature of the anxiety experienced by patients with GAD, shortacting benzodiazepines such as alprazolam are not especially helpful unless dosed 3-4 times per day. Instead, we prefer long-acting agents such as clonazepam. When used to treat GAD, clonazepam should be started at a low dose (0.25-0.5 mg/day) and titrated to higher doses (1-4 mg/day) if clinically necessary. 

Started at 15-20mg/day, the ultimate therapeutic range is 30-60mg/day administered in two to three divided daily doses. Refer to Section 5.1.4 for more information regarding buspirone. 

Pharmacokinetics Buspirone is rapidly absorbed and undergoes extensive first-pass metabolism. Approximately 95% of buspirone is plasma protein bound. In a single dose study, 29% to 63% of the dose was excreted in the urine within 24 hours. 

Grapefruityw/ce- Coadministration of buspirone (10 mg as a single-dose) with... 

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... 

Buspirone (BuSpar) is the first example of a class of anxiolytic agents that can relieve some symptoms of anxiety in doses that do not cause sedation. Buspirone is structurally unrelated to existing psychotropic drugs. 

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. 

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. 

Mayol, R.F., Adamson, D.S., Gammans, R.E., and LaBudde, J.A. (1985) Pharmacokinetics and disposition of 14C-buspirone HCl after intravenous and oral dosing in man. Clin Pharmacol Ther... 

Buspirone. At higher doses, buspirone modulates serotonergic activity and acts as a dopamine antago-... 

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