Browse Prescribing Notes by Therapeutic Subcategory

BENZODIAZEPINES (eg, alprazolam, lorazepam): Benzodiazepines are believed to exert their anxiolytic effects through enhancement of the GABA-benzodiazepine receptor complex. Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the CNS that acts on specific receptor subtypes GABA_A, the receptor involved in sedation and anxiolytic action, and GABA_B. Benzodiazepines bind nonspecifically to GABA_A receptors, which may contribute to their anxiolytic effects.

There is evidence that tolerance develops to the sedative effects of benzodiazepines. Abrupt discontinuation should be avoided and a gradual dosage-tapering schedule should be employed after extended therapy. Withdrawal symptoms can appear following cessation of recommended doses after as little as one week of therapy.

SELECTIVE SEROTONIN REUPTAKE INHIBITORS: Selective serotonin reuptake inhibitors (SSRIs) (eg, fluoxetine, sertraline) potentiate serotonergic activity by inhibiting neuronal reuptake of serotonin (5-HT). Increased serotonergic activity in the CNS reduces noradrenergic activity producing anxiolytic effects. SSRIs produce greater anxiolytic effects than agents that inhibit reuptake of both serotonin and norepinephrine. SSRIs are also shown to be an effective treatment for obsessive-compulsive disorder (OCD) with less potential for side effects than TCAs. SSRIs have a low affinity for adrenergic and muscarinic receptors and have less sedative, anticholinergic, and cardiovascular effects than tricyclic antidepressants. Dosage tapering is preferred to abrupt discontinuation to avoid withdrawal symptoms. Concomitant administration of SSRIs with other serotonergic medications may cause serotonin syndrome.

SEROTONIN AND NOREPINEPHRINE REUPTAKE INHIBITORS: Serotonin and norepinephrine reuptake inhibitors (SNRIs) (eg, duloxetine, venlafaxine) produce their anxiolytic effect by inhibiting neuronal reuptake of serotonin and norepinephrine. Like the SSRIs, SNRIs have a low affinity for adrenergic, histaminic, and muscarinic receptors and have similar side effect profiles to SSRIs.

TRICYCLIC ANTIDEPRESSANTS: The anxiolytic effect of tricyclic antidepressants (TCAs) is not fully understood. Tricyclic antidepressants block neuronal reuptake of norepinephrine and serotonin. In general, secondary amine tricyclics (eg, nortriptyline) more selectively inhibit the reuptake of norepinephrine whereas tertiary amine tricyclics (eg, doxepin, clomipramine) inhibit both norepinephrine and serotonin. Tertiary amine tricyclics tend to be more sedating and have greater anticholinergic effects than secondary amine tricyclics. Tolerance to these effects may develop with continued use.

OTHER CLASSES: Azapirones (eg, buspirone) appear to exert their anxiolytic effects by increasing serotonergic activity through partial agonism of the receptor subtype 5-HT_1A and weak antidopaminergic activity. There is a lack of cross tolerance between azapirones and benzodiazepines. Antihistamines (eg, hydroxyzine) are effective treatment alternatives for anxiety disorders, but only at doses that produce marked sedation.