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Table 25 2 Benzodiazepine interactions with other drugs
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Drug Antacids Cimetidine Contraceptives Digoxin Disulfiram Isoniazid Levodopa Propoxyphene Rifampin Warfarin Effects Decreased absorption of benzodiazepines Increased half-life of diazepam and triazolam Increased levels of diazepam and triazolam Alprazolam and diazepam raise digoxin level Increased duration of action of sedatives Increased plasma diazepam Inhibition of antiparkinsonism effect Impaired clearance of diazepam Decreased plasma diazepam Decreased prothrombin time
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primarily as an anti-obsessional augmenting agent for the SSRI drugs There is some evidence that antipsychotics may be helpful as adjuncts to the SSRIs in treatment-resistant cases Psychosurgery has a limited place in selected cases of severe unremitting OCD The stereotactic techniques now being used, including modified cingulotomy, are great improvements over the crude methods of the past
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causing hepatic microsomal enzyme stimulation (not the case with benzodiazepines), which may affect the metabolism of other medications 2 Panic attacks Panic attacks may be treated in several ways A sublingual dose of lorazepam (05 2 mg) or alprazolam (05 1 mg) is often effective for urgent treatment For sustained treatment, SSRIs are the initial drugs of choice (adequate blood levels will require dosages similar to those used in the treatment of depression) For example, sertraline starting at 25 mg/d and increased after 1 week to 50 mg/d may be effective Because of initial agitation in response to antidepressants, doses should start low and be very gradually increased High-potency benzodiazepines may be used for symptomatic treatment as the antidepressant dose is titrated upward Clonazepam (1 6 mg/d orally) and alprazolam (05 6 mg/d orally) are effective alternatives to antidepressants Both drugs may produce marked withdrawal if stopped abruptly and should always be tapered Because of chronicity of the disorders and the problem of dependency with benzodiazepine drugs, it is generally desirable to use antidepressant drugs as the principal pharmacologic approach Antidepressants have been used in conjunction with -blockers in resistant cases Propranolol (40 160 mg/d orally) can mute the peripheral symptoms of anxiety without significantly affecting motor and cognitive performance They block symptoms mediated by sympathetic stimulation (eg, palpitations, tremulousness) but not nonadrenergic symptoms (eg, diarrhea, muscle tension) Contrary to current belief, they usually do not cause depression as a side effect and can be used cautiously in patients with depression Valproate has been found to be as effective in panic disorder as the antidepressants and is another useful alternative 3 Phobic disorder Phobic disorder may be part of the panic disorder and is treated within that framework Global social phobias may be treated with SSRIs, such as paroxetine, sertraline, and fluvoxamine, or monoamine oxidase (MAO) inhibitors in the same dosage as used for depression Gabapentin, an anticonvulsant with anxiolytic properties, may be an alternative to antidepressants in the treatment of social phobia in a dosage of 300 3600 mg/d, depending on response versus sedation Specific phobias such as performance anxiety may respond to moderate doses of -blockers, such as propranolol, 20 40 mg 1 hour prior to exposure A sustained effect is often not obtained with drugs alone; a combination of drugs, behavioral techniques, and cognitive psychotherapy is most effective If there is any indication of seizure-like phenomena, carbamazepine or valproic acid should be considered 4 Obsessive-compulsive disorder OCD responds to serotonergic drugs in about 60% of cases and usually requires a longer response time than for depression (up to 12 weeks) Clomipramine has proved effective in doses equivalent to those used for depression Fluoxetine (an SSRI drug) has been widely used in this disorder but in doses higher than those used in depression (up to 60 80 mg/d) The other SSRI drugs such as sertraline, paroxetine, and fluvoxamine are being used with comparable efficacy, each with its own side-effect profile Buspirone in doses of 15 60 mg/d appears to be effective
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