Alprazolam dosing

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... 

Alprazolam dose should be reduced by 50% if nefazodone (Serzone) or fluvoxamine is added. 

Some evidence indicates that patients maintained on alprazolam therapy may require lower doses than those used initially. As noted earlier, Nagy et al. ( 35) found that many patients sustained their improvement with lower dosages, and others have reported similar findings ( 32, 38). By contrast, Rashid et al. (39) found an increase in alprazolam dose over time. 

Increased depressive effects when taken with other CNS depressants Inhibitors of CYP450 3A, such as nefazodone, fluvoxamine, fluoxetine, and even grapefruit juice, may decrease clearance of alprazolam and thereby raise alprazolam plasma levels and enhance sedative side effects alprazolam dose may need to be lowered... 

Adding fluvoxamine, fluoxetine, or nefazodone can increase alprazolam levels and make the patient very sleepy unless the alprazolam dose Is lowered by half or more... 

Clinical experience suggests that alprazolam can be particularly difficult to taper when lower doses are reached (e.g., tapering from 1 to 0 mg) (Ciraulo et al. 1990). One possible explanation for this is suggested by data from an animal model showing that alprazolam at doses of 0.02—0.05 mg/kg increases benzodiazepine receptor number above baseline (Miller et al. 1987). When difficulty is encountered in tapering the last 1—2 mg of alprazolam, the rate of dose reduction can be decreased to 0.25 mg/week, and/or adjunctive medication may... 

Miller LG, Greenblatt DJ, Barnhill JG, et ah Benzodiazepine receptor binding of tri-azolobenzodiazepines in vivo increased receptor number with low-dose alprazolam. J Neurochem 49 1595-1601, 1987... 

Pregabalin produced anxiolytic effects similar to lorazepam, alprazolam, and venlafaxine in acute trials. Sedation and dizziness were the most common adverse effects, and the dose should be tapered over 1 week upon discontinuation. 

Alprazolam and clonazepam are the most frequently used of the BZs and are well accepted by patients. Therapeutic response typically occurs in 1 to 2 weeks. With alprazolam, the duration of action may be as little as 4 to 6 hours with breakthrough symptoms between dosing. The use of extended-release alprazolam or clonazepam avoids this problem. 

The starting dose of alprazolam is 0.25 to 0.5 mg three times daily (or 0.5 mg once daily of alprazolam extended release), slowly increasing over several weeks to an ideal dose. Most patients require 3 to 6 mg/day. 

Signs and symptoms of BZ withdrawal are similar to those of alcohol withdrawal, including muscle pain, anxiety, restlessness, confusion, irritability, hallucinations, delirium, seizures, and cardiovascular collapse. Withdrawal from short-acting BZs (e.g., oxazepam, lorazepani, alprazolam) has an onset within 12 to 24 hours of the last dose. Diazepam, chlordiazep-oxide, and clorazepate have elimination half-lives (or active metabolites with elimination half-lives) of 24 to greater than 100 hours. So, withdrawal may be delayed for several days after their discontinuation. 

The onset of withdrawal from long-acting BZs may be up to 7 days after discontinuation of the drug. Detoxification is approached by initiating treatment at usual doses and maintaining this dose for 5 days. The dose is then tapered over 5 days. Alprazolam withdrawal may require a more gradual taper. 

Substance-Induced Anxiety Disorder. Numerous medicines and drugs of abuse can produce panic attacks. Panic attacks can be triggered by central nervous system stimulants such as cocaine, methamphetamine, caffeine, over-the-counter herbal stimulants such as ephedra, or any of the medications commonly used to treat narcolepsy and ADHD, including psychostimulants and modafinil. Thyroid supplementation with thyroxine (Synthroid) or triiodothyronine (Cytomel) can rarely produce panic attacks. Abrupt withdrawal from central nervous system depressants such as alcohol, barbiturates, and benzodiazepines can cause panic attacks as well. This can be especially problematic with short-acting benzodiazepines such as alprazolam (Xanax), which is an effective treatment for panic disorder but which has been associated with between dose withdrawal symptoms. 

Benzodiazepines. The introduction of the benzodiazepines represented a significant advance in the treatment of panic disorder. In contrast to MAOIs and TCAs, the benzodiazepines begin to provide relief the very first day of treatment, and many patients experience a complete response by the end of the second week of therapy. All benzodiazepines should theoretically alleviate the symptoms of a panic attack at comparable doses, but the benzodiazepines of choice are alprazolam (Xanax, Xanax XR) and clonazepam (Klonopin). It likely is not coincidental that these two are among the highest potency benzodiazepines. However, they differ considerably from a pharmacokinetic standpoint. If clonazepam is the tortoise of benzodiazepines, then alprazolam is the hare. 

When initiating benzodiazepine treatment for GAD, tolerability can be improved by starting at a low dose and gradually titrating to the effective dose range over the course of several days. Most patients with GAD respond well to l-3mg/day of extended-release alprazolam, l-2mg/day of clonazepam, or 10-20mg/day of diazepam. Elderly patients often do best at approximately half these daily doses. 

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. 

Benzodiazepines. The best studied of the benzodiazepines for social anxiety disorder, clonazepam has been demonstrated in controlled trials to be effective during both acute treatment (at an average dose of 2.4mg/day) and long-term maintenance therapy lasting up to 2 years. A controlled study of another high potency benzodiazepine, alprazolam, also proved effective, though it was outperformed by the MAOI antidepressant phenelzine and exhibited response rates lower than those reported with clonazepam. 

Clonazepam should initially be administered at 0.25-1 mg/day and titrated every 3-7 days to an effective dose of 0.5-4 mg/day in one to two daily doses. Shorter-acting alprazolam is initiated at 0.5-1 mg/day in two to four divided daily doses and titrated to 1-8 mg/day in two to four divided daily doses. The extended release formulation of alprazolam permits less frequent dose administration. Initiating the benzodiazepines at a low dose and titrating in a stepwise fashion minimizes the potential for excessive sedation during treatment initiation. 

Specific Sociai Anxiety Disorder, Acute Phase Treatment. Different strategies have evolved for treating specific social anxiety disorder versus generalized social anxiety disorder. Less complicated is the management of the specific subtype. Exposure-based psychotherapy is a mainstay of treatment, and as-needed medication doses prior to scheduled performances are also widely used. Preferred agents for performance anxiety are alprazolam or propranolol. 

Benzodiazepines. Like the barbiturates, benzodiazepines bind to the GABA receptor and are therefore cross-tolerant with alcohol. As a result, they also make suitable replacement medications for alcohol and are widely used for alcohol detoxification. Theoretically, any benzodiazepine can be used to treat alcohol withdrawal. However, short-acting benzodiazepines such as alprazolam (Xanax) are often avoided because breakthrough withdrawal may occur between doses. Intermediate to long-acting benzodiazepines including chlordiazepoxide (Librium), diazepam (Valium), oxazepam (Serax), lorazepam (Ativan), and clonazepam (Klonopin) are more commonly utilized. 

Aprepitant (Emend) [Centrally Acting Antiemetic] Uses Pre-vents N/V assoc w/ emetogenic CA chemo (eg, cisplatin) (use in combo w/ other antiemetics) Action Substance P/neurokinin l(NKi) receptor antagonist Dose 125 mg PO day 1, 1 h before chemo, then 80 mg PO qAM days 2 3 Caution [B, /-] Contra Use w/ pimozide, Disp Caps SE Fatigue, asthenia, hiccups Interactions T Effects W/ clarithromycin, diltiazem, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, troleandomycin T effects OF alprazolam, astem-izole, cisapride, dexamethasone, methylprednisolone, midazolam, pimozide, terfe-nadine, triazolam, chemo agents, eg, docetaxel, etoposide, ifosfamide, imatinib, irinotecan, paclitaxel, vinblastine, vincristine, vinorelbine i effects W/ paroxetine,... 

WARNING Fatal Hep liver failure possible do not retreat closely monitor for worsening depression or emergence of suicidality, particularly in ped pts Uses Depression Action Neuronal uptake of serotonin norepinephrine Dose Initial 100 mg PO bid usual 300-600 mg/d in 2 doses Caution [C, ] Contra w/ MAOIs, pimozide, carbamazepine, alprazolam active liver Dz Disp Tabs SE Postural 4- BP allergic Rxns HA, drowsiness, xerostomia, constipation, GI upset, liver... 

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