An alternative to benzodiazepines for anxiety

Azapirones: an alternative to benzodiazepines for anxiety

Roger J. Cadieux

The azapirones are a unique pharmacologic class of psychotropic drugs. Buspirone (BuSpar), the first azapirone introduced into clinical practice, as approved in the United States in 1986. Other azapirones still in clinical trials include ipsapirone and tandospirone.[1]

The azapirones are the first effective alternative to benzodiazepines for the treatment of anxiety to have been introduced in nearly three decades.[2] Benzodiazepines have been the mainstay of anxiolytic drug therapy for many years. Although they are generally safe and effective, concerns have been expressed regarding their potential for abuse and addiction, cognitive and functional impairment, withdrawal symptoms and interaction with alcohol.[3]

Azapirones have anxiolytic efficacy similar to that of the benzodiazepines,[4,5] with a better safety profile.[2,6-8] Unlike the benzodiazepines, azapirones have no sedative, muscle relaxant or anticonvulsant properties; no significant abuse potential or withdrawal effects; no cognitive, memory or psychomotor impairment properties; no significant withdrawal symptoms; negligible overdose toxicity; no respiratory depressant properties; no serious drug interaction effects,[7] and no anticholinergic or cardiotoxic effects[8] (Table 1 .[2,7-9] Azapirones have the additional benefit of being well-tolerated by elderly patients.[2]




Buspirone has also demonstrated usefulness in treating a major depressive disorder, both as a primary treatment[15] and as an adjunct to antidepressants, particularly the SSRIs.[8,9,15] Clinical experience and a number of published reports indicate that augmenting standard antidepressants with buspirone serves to either enhance response or convert nonresponders to responders.[9] Buspirone is also effective when anxiety and depression coexist,[8,9,15] probably the most common psychiatric condition seen by primary care physicians.[17]

When buspirone is used as a primary treatment for depression, the required daily dosage appears to be high, in the range of 40 to go Mg.[15] High dosages of buspirone may be impractical because of the large number of pills needed each day, the high cost and the increased likelihood of side effects. However, when buspirone is used to augment antidepressants in the management of severe and treatment-resistant depression, a moderate dosage of buspirone (30 mg per day) appears useful.[13]


Because elderly patients are more vulnerable to drug side effects such as sedation and orthostatic hypotension, use of long-acting benzodiazepines, which are more likely to produce sedation and falls than the azapirones, is discouraged by OBRA (Omnibus Budget Reconciliation Act) nursing home regulations. Many physicians have turned to buspirone for treating elderly patients with chronic anxiety or anxiety with depressive symptoms. The recommended geriatric dosage for treatment of these disorders is between 20 and 30 mg per day in divided doses.[10] To reduce the possibility of side effects, buspirone should be started in a dosage of 5 mg three times per day and gradually increased to 10 mg three times per day over a course of seven to 14 days.

Buspirone is also recommended as first line treatment for chronic agitation with dementia, at an average dosage of 30[18], to 35 mg per day.[10] Higher dosages (to 60 mg per day) may be required for full therapeutic effectiveness.[10] Side effects experienced by demented geriatric patients taking buspirone are typically milder than those experienced with SSRIs. The side effects of buspirone include lightheadedness, dizziness, nausea and paradoxic stimulation.[10] If any of these effects occur, the buspirone dosage can be lowered.

When taken with neuroleptic drugs, buspirone (60 mg per day) has been shown to decrease the severity of tardive dyskinesia and improve neuroleptic-induced akathisia and parkinsonism in some patients.[9,19]


In addition to its antianxiety and antidepressant effects, buspirone has been found to have a number of other therapeutic benefits. Buspirone reduces aggressiveness and irritability in patients with brain injury or other organic brain disorders, in patients with dementia, and in children with developmental disability, mental retardation and autism.[9]

Buspirone augmentation of tricyclic antidepressants and SSRIs appears to be use”, in patients with obsessive-compulsive disorder. A dosage of 30 to 60 mg per day was reported to be helpful in some patients with refractory obsessive-compulsive disorder, although some patients experienced worsening of symptoms.[9,19,20]

A small number of reports note positive effects from buspirone in the treatment of a wide variety of other disorders, including post-traumatic stress syndrome, social phobia, premenstrual syndrome, smoking cessation and migraine headaches,[15] as well as attention-deficit hyperactivity disorder[21] and irritable bowel syndrome,[8] and in the treatment of type-A cardiac patients.[22]

Finally, buspirone appears to be particularly useful in the treatment of alcoholics with anxiety because of its low abuse potential. Buspirone therapy in anxious alcoholics was found to be associated with not only reduced anxiety but also a slower return to alcohol consumption and fewer drinking days during the follow-up period of a 12-week study.[23] The role of 5-HT in appetite dysfunctions may explain reports that buspirone reduces the craving for alcohol in alcohol-dependent patients.[13]


[1.] Eison AS. Azapirones: history of development. J Clin Psychopharmacol 1990;10(3 Suppl):2-5. [2.] Napoliello MJ, Domantay AG. Buspirone: a world-wide update. Br J Psychiatry 1991;159(Suppl 12):40-4. [3.] Eison MS. Azapirones: clinical uses of serotonin partial agonists. Fam Pract Recertification 1989;11(Suppl):8-16. [4.] Rickels K, Schweizer E. The clinical course and long-term management of generalized anxiety disorder. J Clin Psychopharmacol 1990;10(3 Suppl): 101-10. [5.] Goldberg HL, Finnerty RJ. The comparative efficacy of buspirone and diazepam in the treatment of anxiety. Am J Psychiatry 1979;136:1184-7. [6.] Sellers EM, Schneiderman, Romach MK, Kaplan HL, Somer GR. Comparative drug effects and abuse liability of lorazepam, buspirone and seco-barbital in nondependent subjects. J Clin Psychopharmacol 1992;12:79-85. [7.] Baughman OL. The safety record of buspirone in generalized anxiety disorder. In: Buspirone: seven-year update [Monograph]. Memphis: Physicians Postgraduate Press, 1994:37-43. [8.] Rickels K, Amsterdam JD, Clary C, Puzzuoli G, Schweizer E. Buspirone in major depression: a controlled study. J Clin Psychiatry 1991;52:34-8. [9.] Sussman N. The uses of buspirone in psychiatry. In: Buspirone: seven-year update [Monograph]. Memphis: Physicians Postgraduate Press, 1994; 12(l):3-19. [10.] Weiss KJ. Management of anxiety and depression syndromes in the elderly. J Clin Psychiatry 1994;55(Suppl):5-12. [11.] Red book update. Montvale, N.J.: Medical Economics, 1995;14(4):6,12,60. [12.] Eison MS. Serotonin: a common neurobiologic substrate in anxiety and depression. J Clin Psychopharmacol 1990;10(3 Suppl):26-30. [13.] Dubovsky SL. Beyond the serotonin reuptake inhibitors: rationales for the development of new serotonergic agents. J Clin Psychiatry 1994; 55(Suppl):34-44. [14.] Rickels K. Buspirone in clinical practice. J Clin Psychiatry 1990;51(Suppl):51-4. [15.] Schweizer E, Rickels K. New and emerging clinical uses for buspirone. In: Buspirone: seven-year update [Monograph]. Memphis: Physicians Postgraduate Press, 1994:46-54. [16.] Temple DL Jr, Yevich JP, New JS. Buspirone: chemical profile of a new class of anxioselective agents. J Clin Psychiatry 1982;43(12 Pt 2):4-9. [17.] Barrett JE, Barrett JA, Oxman TE, Gerber PD. The prevalence of psychiatric disorders in a primary care practice. Arch Gen Psychiatry 1988;45:1100-6. [18.] Kunik ME, Yudofsky SC, Silver JM, Hales RE. Pharmacologic approach to management of agitation associated with dementia. J Clin Psychiatry 1994;55(Suppl):13-7. [19.] Goldberg RJ. The use of buspirone in geriatric patients. In: Buspirone: seven-year update [Monograph]. Memphis: Physicians Postgraduate Press, 1994:31-5. [20.] Hollander E, Cohen LJ. The assessment and treatment of refractory anxiety. J Clin Psychiatry 1994;55(Suppl):27-31. [21.] McCormick LH, Rizzuto GT, Knuckles HB. A pilot study of buspirone in attention-deficit hyperactivity disorder. Arch Fam Med 1994;3:68-70. [22.] Littman AB, Fava M, McKool K, Lamon-Fava S, Pegg E. Buspirone therapy for type A behavior, hostility, and perceived stress in cardiac patients. Psychother Psychosom 1999;59:107-10. [23.] Kranzler HR, Burleson JA, Del Boca FK, Babor TF, Korner P, Brown J, et al. Buspirone treatment of anxious alcoholics. A placebo-controlled trial. Arch Gen Psychiatry 1994;51:720-31.

RICHARD W. SLOAN, M.D., R.PH., coordinator of this series is chairman and residency program director of the Department of Family Medicine at York (Pa.) Hospital and clinical associate professor in family and community medicine at the Milton S, Hershey Medical Center, Pennsylvania State University, Hershey, Pa.

The Author

Roger J. Cadieux, M.D. is associate professor of Psychiatry and director of the Geriatric Assessment Program in the Department of Psychiatry, Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, Pa. Dr. Cadieux received his medical degree from Louisiana State University School of Medicine in Shreveport and completed a psychiatry residency at Pennsylvania State University College of Medicine.

Address correspondence to Roger 1. Cadieux, M.D., Suite 38, Northwood Office Center, 2215 Forest Hills Dr., Harrisburg, PA 17112.

COPYRIGHT 1996 American Academy of Family Physicians

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