Buspirone Benzodiazepines

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. 

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. 

Generalized anxiety Duloxetine Escitalopram Paroxetine Venlafaxine XR Benzodiazepines Buspirone Imipramine Sertraline Hydroxyzine Pregabalin... 

A therapeutic alternative for treatment of anxiety and depression is the use of 5-HT1A agonists. Azapirones comprise the major class of 5-HT1A agonists of which buspirone (Buspar [4]) is the only FDA-approved 5-HT1A selective agonist (relative to the other 13 serotonin receptor subtypes) for anxiety currently on the US market (Scheme 19.1). Buspirone has shown efficacy in randomized controlled trials of GAD for which it was approved [5-7]. Unlike benzodiazepines, buspirone is not addictive... 

Buspirone (Buspar). The first nonsedating, nonbenzodiazepine specifically introduced as an anxiolytic, buspirone is FDA approved for the treatment of GAD. This medication acts as a partial agonist at the postsynaptic serotonin (5HT)-1A receptor. Like the antidepressants, buspirone has a delayed onset of action and effectively relieves the intrapsychic symptoms of GAD. Devoid of the muscle-relaxing properties of benzodiazepines, buspirone does not as effectively relieve the physical symptoms of GAD. Buspirone is not effective in the treatment of depression. Furthermore, its utility for the treatment of anxiety disorders other than GAD appears to be limited. 

Drugs that affect nefazodone include general anesthetics, sibutramine, sumatriptan, buspirone, carbamazepine, and propranolol. Drugs that may be affected by nefazodone include alcohol, benzodiazepines, buspirone, carbamazepine, cisapride, digoxin, haloperidol, HMG-CoA reductase inhibitors, MAOIs, propranolol, St. John s wort, cyclosporine, and tacrolimus. 

Clarithromycin Drugs that may be affected by clarithromycin include anticoagulants, benzodiazepines, buspirone, carbamazepine, cisapride, cyclosporine, digoxin. 

Drugs that may be affected by itraconazole include alfentanil, almotriptan, alprazolam, amphotericin B, aripiprazole, benzodiazepines, buspirone, busulfan, calcium blockers, carbamazepine, cilostazol, cisapride, corticosteroids, cyclosporine, digoxin, disopyramide, docetaxel, dofetilide, eletriptan, epierenone, ergot alkaloids, haloperidol, HMG-CoA reductase inhibitors, hydantoins (phenytoin), hypoglycemic agents, oral midazolam, phosphodiesterase type 5 inhibitors, pimozide, polyenes, protease inhibitors, quinidine, rifamycins, sirolimus, tacrolimus, tolterodine, triazolam, trimetrexate, vinca alkaloids, warfarin, and zolpidem. 

Recommended drugs for GAD are antidepressants, benzodiazepines, Buspirone and hydroxyzine (Ballenger et al. 2001). The use of antipsychotics is not supported by controlled trials and is discouraged due to their poor long-term... 

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. 

Chouinard, G., Lefko-Singh, K., and Teboul, E. (1999) Metabolism of anxiolytics and hypnotics benzodiazepines, buspirone, zopli-cone, and zolpidem. Cell Mol Neurobiol 19 533—552. 

Buspirone has been shown to be as effective as benzodiazepines for the treatment of GAD. However, it appears to take several weeks for this drug to be effective. The big advantage of using buspirone instead of benzodiazepines is that buspirone does not have the sedative effect, physical dependence, and withdrawal symptoms often seen with benzodiazepines. Buspirone does, however, cause stomach upset in some patients that may discourage patients from taking the drug. 

Buspirone. Several comparative studies of buspirone and benzodiazepines have reported comparable efficacy in reducing symptoms of anxiety. However, in contrast to benzodiazepines, buspirone is devoid of significant sedative or euphoric effects. Treatment with buspirone and other azaperones, such as gepirone, ipsapirone, and tandospirone, does not result in abuse, addiction, dependence, or withdrawal symptoms [Keppel Hesselink 1992). Buspirone also spares both cognitive and psychomotor performance [N. Sussman 1994). 

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]. 

In this chapter, we discuss the pharmacology of medications that are classified as anxiolytic, sedative, or hypnotic—primarily the benzodiazepines, buspirone, zolpidem, eszopiclone, and zale-plon. Subsequently, we present diagnosis-specific treatment guidelines (outlined in Table 3-1). The commonly used anxiolytics and hypnotics, together with their usual doses, are shown in Table 3-2. Many antidepressant medications are also effective in the treatment of anxiety disorders. The pharmacology of antidepressants is discussed in Chapter 2 their clinical use in anxiety disorders is addressed in the diagnosis-specific sections later in this chapter. 

Social phobia SSRIs, MAOIs, benzodiazepines, buspirone, venlafaxine... 

Generahzed anxiety disorder can be treated with benzodiazepines, buspirone, and certain antidepressants (e.g., venlafaxine, paroxetine, escitalopram). These agents are compared in Table 3-3. 

Unlike benzodiazepines, buspirone is not associated with sedative or abuse problems, but some clinicians have observed that bus-pirone s anxiolytic properties do not appear to be as potent as those of benzodiazepines, particularly in patients who have previously received a benzodiazepine. Because buspirone is not sedating and has no psychomotor effects, it has a distinct advantage over benzodiazepines when optimal alertness and motor performance are necessary. Response to buspirone occurs in approximately 2-4 weeks. Buspirone does not show cross-tolerance with benzodiazepines and other sedative or hypnotic drugs such as alcohol, barbiturates, and chloral hydrate. Therefore, buspirone does not suppress benzodiazepine withdrawal symptoms. In anxious patients who are taking a benzodiazepine and who require a switch to buspirone, the benzodiazepine must be tapered gradually to avoid withdrawal symptoms, despite the fact that the patient is receiving buspirone. 

TABLE 3-3. Comparison of benzodiazepines, buspirone, and antidepressants for the treatment of anxiety ... 

Area of assessment Benzodiazepines and related drugs Non-benzodiazepines (buspirone)... 

Buspirone causes less psychomotor impairment than diazepam and does not affect driving skills. The drug does not potentiate the central nervous system depressant effects of conventional sedative-hypnotic drugs, ethanol, or tricyclic antidepressants, and elderly patients do not appear to be more sensitive to its actions. Tachycardia, palpitations, nervousness, gastrointestinal distress, and paresthesias may occur more frequently than with benzodiazepines. Buspirone also causes a dose-dependent pupillary constriction. Blood pressure may be elevated in patients receiving MAO inhibitors. A number of buspirone analogs have been developed (eg, ipsapirone, gepirone, tandospirone) and are under study. 

Compared with benzodiazepines, buspirone causes less sedation and memory impairment (9), has little interaction with alcohol (2,10), and is essentially devoid of problems of abuse, disinhibition, tolerance, and dependence. 

The atypical antianxiety medication buspirone has been used with some success with GAD patients. This medication offers the benefits of reduced rumination and worry, but without the problems of sedation and potential drug dependence seen with benzodiazepines. Buspirone is not addictive and thus provides a treatment option for GAD patients with substance abuse risk. 

Because antipsychotic therapy has shown only modest efficacy and poses a substantial risk of undesirable side effects, medications traditionally used to treat disruptive behaviors and aggression in other psychiatric and neurologic disorders have been suggested as potential alternatives. These alternatives include benzodiazepines, buspirone, carbamazepine, selegiline, and SSRls. 

Buspirone s anxiolytic mechanism of action is unknown. It is thought to exert its anxiolytic effect through 5-HTia partial agonist activity at the presynaptic 5-HT receptors by reducing the firing of 5-HT neurons. Unlike benzodiazepines, buspirone is effective for the cognitive symptoms of anxiety. ... 

Other adverse effects Barbiturates and carbamates (but not benzodiazepines, buspirone, zolpidem, or zaleplon) induce the formation of the liver microsomal enzymes that metabolize dmgs. This enzyme induction may lead to multiple drug interactions. Barbiturates may also precipitate acute intermittent porphyria in susceptible patients. Chloral hydrate may displace coumarins from plasma protein binding sites and increase anticoagulant effects. 

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