Other Warnings/Precautions

• Dosage changes should be made in collaboration with prescriber

• Use with caution in patients with pulmonary disease; rare reports of death after initiation of benzodiazepines in patients with severe pulmonary impairment

• History of drug or alcohol abuse often creates greater risk for dependency

• Hypomania and mania have occurred in depressed patients taking alprazolam

• Use only with extreme caution if patient has obstructive sleep apnea

• Some depressed patients may experience a worsening of suicidal ideation

• Some patients may exhibit abnormal thinking or behavioral changes similar to those caused by other CNS depressants (i.e., either depressant actions or disinhibiting actions)

Do Not Use

• If patient has angle-closure glaucoma

• If patient is taking ketoconazole or itraconazole (azole antifungal agents)

• If there is a proven allergy to alprazolam or any benzodiazepine

ALPRAZOLAM: SPECIAL POPULATIONS

Renal Impairment

• Drug should be used with caution

Hepatic Impairment

• Should begin with lower starting dose (0.5–0.75 mg/day in 2 or 3 divided doses)

Cardiac Impairment

• Benzodiazepines have been used to treat anxiety associated with acute myocardial infarction

Elderly

• Should begin with lower starting dose (0.5–0.75 mg/day in 2 or 3 divided doses) and be monitored closely

Children and Adolescents

• Safety and efficacy not established but often used, especially short-term and at the lower end of the dosing scale

• Long-term effects of alprazolam in children/adolescents are unknown

• Should generally receive lower doses and be more closely monitored

Pregnancy

• Risk Category D [positive evidence of risk to human fetus; potential benefits may still justify its use during pregnancy]

• Possible increased risk of birth defects when benzodiazepines taken during pregnancy

• Because of the potential risks, alprazolam is not generally recommended as treatment for anxiety during pregnancy, especially during the first trimester

• Drug should be tapered if discontinued

• Infants whose mothers received a benzodiazepine late in pregnancy may experience withdrawal effects

• Neonatal flaccidity has been reported in infants whose mothers took a benzodiazepine during pregnancy

• Seizures, even mild seizures, may cause harm to the embryo/fetus

Breast Feeding

• Some drug is found in mother’s breast milk

✽ Recommended either to discontinue drug or bottle feed

• Effects on infant have been observed and include feeding difficulties, sedation, and weight loss

ALPRAZOLAM: THE ART OF PSYCHOPHARMACOLOGY

Potential Advantages

• Rapid onset of action

• Less sedation than some other benzodiazepines

• Availability of an XR formulation with longer duration of action

Potential Disadvantages

• Euphoria may lead to abuse

• Abuse especially risky in past or present substance abusers

Primary Target Symptoms

• Panic attacks

• Anxiety

Pearls

✽ One of the most popular benzodiazepines for anxiety, especially among primary care physicians and psychiatrists

• Is a very useful adjunct to SSRIs and SNRIs in the treatment of numerous anxiety disorders

• Not effective for treating psychosis as a monotherapy, but can be used as an adjunct to antipsychotics

• Not effective for treating bipolar disorder as a monotherapy, but can be used as an adjunct to mood stabilizers and antipsychotics

• May both cause depression and treat depression in different patients

• Risk of seizure is greatest during the first 3 days after discontinuation of alprazolam, especially in those with prior seizures, head injuries, or withdrawal from drugs of abuse

• Clinical duration of action may be shorter than plasma half-life, leading to dosing more frequently than 2–3 times daily in some patients, especially for immediate release alprazolam

• 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

• When using to treat insomnia, remember that insomnia may be a symptom of some other primary disorder itself, and thus warrant evaluation for comorbid psychiatric and/or medical conditions

✽ Alprazolam XR may be less sedating than immediate-release alprazolam

✽ Alprazolam XR may be dosed less frequently than immediate-release alprazolam, and lead to less interdose breakthrough symptoms and less “clock-watching” in anxious patients

• Slower rises in plasma drug levels for alprazolam XR have the potential to reduce euphoria/abuse liability, but this has not been proven

• Slower falls in plasma drug levels for alprazolam XR have the potential to facilitate drug discontinuation by reducing withdrawal symptoms, but this has not been proven

✽ Alprozolam XR generally has longer biological duration of action than clonazepam

✽ If clonazepam can be considered a “long-acting alprazolam-like anxiolytic,” then alprazolam XR can be considered “an even longer-acting clonazepam-like anxiolytic” with the potential of improved tolerability features in terms of less euphoria, abuse, dependence, and withdrawal problems, but this has not been proven

• Though not systematically studied, benzodiazepines have been used effectively to treat catatonia and are the initial recommended treatment

Suggested Reading

DeVane CL, Ware MR, Lydiard RB. Pharmacokinetics, pharmacodynamics, and treatment issues of benzodiazepines: alprazolam, adinazolam, and clonazepam. Psychopharmacol Bull 1991;27:463–73.

Greenblatt DJ, Wright CE. Clinical pharmacokinetics of alprazolam. Therapeutic implications. Clin Pharmacokinet 1993; 24:453–71.

Jonas JM, Cohon MS. A comparison of the safety and efficacy of alprazolam versus other agents in the treatment of anxiety, panic, and depression: a review of the literature. J Clin Psychiatry 1993;54(Suppl):S25–45.

Klein E. The role of extended-release benzodiazepines in the treatment of anxiety: a risk-benefit evaluation with a focus on extended-release alprazolam. J Clin Psychiatry 2002;63(Suppl 14):S27–33.

Speigel DA. Efficacy studies of alprazolam in panic disorder. Psychopharmacol Bull 1998; 34:191–95.

van Marwijk H, Allick G, Wegman F, Bax A, Riphagen II. Alprazolam for depression. Cochrane Database Syst Rev 2012; 7:CD007139.

AMISULPRIDE

AMISULPRIDE: THERAPEUTICS

Brands

• Solian

see index for additional brand names

Generic?

No

Class

• Atypical antipsychotic (benzamide; possibly a dopamine stabilizer and dopamine partial agonist)

Commonly Prescribed for

(bold for FDA approved)

• Schizophrenia, acute and chronic (outside of U.S., especially Europe)

• Dysthymia

How the Drug Works

• Theoretically blocks presynaptic dopamine 2 receptors at low doses

• Theoretically blocks postsynaptic dopamine 2 receptors at higher doses

✽ May be a partial agonist at dopamine 2 receptors, which would theoretically reduce dopamine output when dopamine concentrations are high and increase dopamine output when dopamine concentrations are low

• Blocks dopamine 3 receptors, which may contribute to its clinical actions

✽ Unlike other atypical antipsychotics, amisulpride does not have potent actions at serotonin 2A or serotonin 1A receptors

✽ Does have antagonist actions at serotonin 7 receptors and serotonin 2B receptors, which may contribute to antidepressant effects