Other Warnings/Precautions

• Use with caution in patients with bipolar disorder unless treated with concomitant mood-stabilizing agent

• Use with caution in patients with urinary retention, benign prostatic hyperplasia, glaucoma, epilepsy

• Use with caution with drugs that lower blood pressure

• When treating children, carefully weigh the risks and benefits of pharmacological treatment against the risks and benefits of nontreatment with antidepressants and make sure to document this in the patient’s chart

• Distribute the brochures provided by the FDA and the drug companies

• Warn patients and their caregivers about the possibility of activating side effects and advise them to report such symptoms immediately

• Monitor patients for activation of suicidal ideation, especially children and adolescents

Do Not Use

• If patient has angle-closure glaucoma

• If patient is taking an MAO inhibitor (except as noted under drug interactions)

• If patient is taking pimozide or thioridazine

• If there is a proven allergy to reboxetine

REBOXETINE: SPECIAL POPULATIONS

Renal Impairment

• Plasma concentrations are increased

• May need to lower dose

Hepatic Impairment

• Plasma concentrations are increased

• May need to lower dose

Cardiac Impairment

• Use with caution

Elderly

• Lower dose is recommended (4–6 mg/day)

• Reduction in the risk of suicidality with antidepressants compared to placebo in adults age 65 and older

Children and Adolescents

• Carefully weigh the risks and benefits of pharmacological treatment against the risks and benefits of nontreatment with antidepressants and make sure to document this in the patient’s chart

• Monitor patients face-to-face regularly, particularly during the first several weeks of treatment

• Use with caution, observing for activation of known or unknown bipolar disorder and/or suicidal ideation, and inform parents or guardians of this risk so they can help observe child or adolescent patients

• No guidelines for children; safety and efficacy have not been established

Pregnancy

• No controlled studies in humans

• Not generally recommended for use during pregnancy, especially during first trimester

• Must weigh the risk of treatment (first trimester fetal development, third trimester newborn delivery) to the child against the risk of no treatment (recurrence of depression, maternal health, infant bonding) to the mother and child

• For many patients this may mean continuing treatment during pregnancy

Breast Feeding

• Some drug is found in mother’s breast milk

• Immediate postpartum period is a high-risk time for depression, especially in women who have had prior depressive episodes, so drug may need to be reinstituted late in the third trimester or shortly after childbirth to prevent a recurrence during the postpartum period

• Must weigh benefits of breast feeding with risks and benefits of antidepressant treatment versus nontreatment to both the infant and the mother

• For many patients, this may mean continuing treatment during breast feeding

REBOXETINE: THE ART OF PSYCHOPHARMACOLOGY

Potential Advantages

• Tired, unmotivated patients

• Patients with cognitive disturbances

• Patients with psychomotor retardation

Potential Disadvantages

• Patients unable to comply with twice daily dosing

• Patients unable to tolerate activation

Primary Target Symptoms

• Depressed mood

• Energy, motivation, and interest

• Suicidal ideation

• Cognitive disturbance

• Psychomotor retardation

Pearls

• May be effective if SSRIs have failed or for SSRI “poop-out”

✽ May be more likely than SSRIs to improve social and work functioning

• Reboxetine is a mixture of an active and an inactive enantiomer, and the active enantiomer may be developed in future clinical testing

✽ Side effects may appear “anticholinergic,” but reboxetine does not directly block muscarinic receptors

• Constipation, dry mouth, and urinary retention are noradrenergic, due in part to peripheral alpha 1 receptor stimulation causing decreased acetylcholine release

✽ Thus, antidotes for these side effects can be alpha 1 antagonists such as tamsulosin, especially for urinary retention in men over 50 with borderline urine flow

• Novel use of reboxetine may be for attention deficit disorder, analogous to the actions of another norepinephrine selective reuptake inhibitor, atomoxetine, but few controlled studies

• Another novel use may be for neuropathic pain, alone or in combination with other antidepressants, but few controlled studies

• Some studies suggest efficacy in panic disorder

Suggested Reading

Eyding D, Lelgemann M, Grouven U, et al. Reboxetine for acute treatment of major depression: systematic review and meta-analysis of published and unpublished placebo and selective serotonin reuptake inhibitor controlled trials. BMJ 2010;341:c4737.

Fleishaker JC. Clinical pharmacokinetics of reboxetine, a selective norepinephrine reuptake inhibitor for the treatment of patients with depression. Clin Pharmacokinet 2000;39(6):413–27.

Kasper S, el Giamal N, Hilger E. Reboxetine: the first selective noradrenaline re-uptake inhibitor. Expert Opin Pharmacother 2000;1(4):771–82.

Keller M. Role of serotonin and noradrenaline in social dysfunction: a review of data on reboxetine and the Social Adaptation Self-evaluation Scale (SASS). Gen Hosp Psychiatry 2001;23(1):15–19.

Tanum L. Reboxetine: tolerability and safety profile in patients with major depression. Acta Psychiatr Scand Suppl 2000;402:37–40.

RISPERIDONE

RISPERIDONE: THERAPEUTICS

Brands

• Risperdal

• CONSTA

see index for additional brand names

Generic?

Yes

Class

• Atypical antipsychotic (serotonin-dopamine antagonist; second generation antipsychotic; also a mood stabilizer)

Commonly Prescribed for

(bold for FDA approved)

• Schizophrenia, ages 13 and older (oral, long-acting microspheres intramuscularly)

• Delaying relapse in schizophrenia (oral)

• Other psychotic disorders (oral)

• Acute mania/mixed mania, ages 10 and older (oral, monotherapy and adjunct to lithium or valproate)

• Autism-related irritability in children ages 5–16

• Bipolar maintenance (long-acting microspheres intramuscularly, monotherapy and adjunct to lithium or valproate)

• Bipolar depression

• Behavioral disturbances in dementias

• Behavioral disturbances in children and adolescents

• Disorders associated with problems with impulse control