Elderly

• Baseline ECG is recommended for patients over age 50

• May be more sensitive to anticholinergic, cardiovascular, hypotensive, and sedative effects

• May require lower dose; it may be useful to monitor plasma levels in elderly patients

• 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

• Not recommended for use in children under age 12

• Not intended for use in children under age 6

• Several studies show lack of efficacy of TCAs for depression

• May be used to treat enuresis or hyperactive/impulsive behaviors

• Some cases of sudden death have occurred in children taking TCAs

• Plasma levels may need to be monitored

• Dose in children generally less than 50 mg/day

• May be useful to monitor plasma levels in children and adolescents

Pregnancy

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

• Crosses the placenta

• Should be used only if potential benefits outweigh potential risks

• Adverse effects have been reported in infants whose mothers took a TCA (lethargy, withdrawal symptoms, fetal malformations)

• Evaluate for treatment with an antidepressant with a better risk/benefit ratio

Breast Feeding

• Some drug is found in mother’s breast milk

✽ Recommended either to discontinue drug or bottle feed

• 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

NORTRIPTYLINE: THE ART OF PSYCHOPHARMACOLOGY

Potential Advantages

• Patients with insomnia

• Severe or treatment-resistant depression

• Patients for whom therapeutic drug monitoring is desirable

Potential Disadvantages

• Pediatric and geriatric patients

• Patients concerned with weight gain

• Cardiac patients

Primary Target Symptoms

• Depressed mood

• Chronic pain

Pearls

• Tricyclic antidepressants are often a first-line treatment option for chronic pain

• Tricyclic antidepressants are no longer generally considered a first-line option for depression because of their side effect profile

• Tricyclic antidepressants continue to be useful for severe or treatment-resistant depression

• Noradrenergic reuptake inhibitors such as nortriptyline can be used as a second-line treatment for smoking cessation, cocaine dependence, and attention deficit disorder

• TCAs may aggravate psychotic symptoms

• Alcohol should be avoided because of additive CNS effects

• Underweight patients may be more susceptible to adverse cardiovascular effects

• Children, patients with inadequate hydration, and patients with cardiac disease may be more susceptible to TCA-induced cardiotoxicity than healthy adults

• For the expert only: although generally prohibited, a heroic but potentially dangerous treatment for severely treatment-resistant patients is for an expert to give a tricyclic/tetracyclic antidepressant other than clomipramine simultaneously with an MAO inhibitor for patients who fail to respond to numerous other antidepressants

• If this option is elected, start the MAOI with the tricyclic/tetracyclic antidepressant simultaneously at low doses after appropriate drug washout, then alternately increase doses of these agents every few days to a week as tolerated

• Although very strict dietary and concomitant drug restrictions must be observed to prevent hypertensive crises and serotonin syndrome, the most common side effects of MAOI and tricyclic/tetracyclic antidepressant combinations may be weight gain and orthostatic hypotension

• Patients on TCAs should be aware that they may experience symptoms such as photosensitivity or blue-green urine

• SSRIs may be more effective than TCAs in women, and TCAs may be more effective than SSRIs in men

• Not recommended for first-line use in children with ADHD because of the availability of safer treatments with better documented efficacy and because of nortriptyline’s potential for sudden death in children

✽ Nortriptyline is one of the few TCAs where monitoring of plasma drug levels has been well studied

• Since tricyclic/tetracyclic antidepressants are substrates for CYP450 2D6, and 7% of the population (especially Caucasians) may have a genetic variant leading to reduced activity of 2D6, such patients may not safely tolerate normal doses of tricyclic/tetracyclic antidepressants and may require dose reduction

• Phenotypic testing may be necessary to detect this genetic variant prior to dosing with a tricyclic/tetracyclic antidepressant, especially in vulnerable populations such as children, elderly, cardiac populations, and those on concomitant medications

• Patients who seem to have extraordinarily severe side effects at normal or low doses may have this phenotypic CYP450 2D6 variant and require low doses or switching to another antidepressant not metabolized by 2D6

Suggested Reading

Anderson IM. Meta-analytical studies on new antidepressants. Br Med Bull 2001;57:161–78.

Anderson IM. Selective serotonin reuptake inhibitors versus tricyclic antidepressants: a meta-analysis of efficacy and tolerability. J Aff Disorders 2000;58:19–36.

Hughes JR, Stead LF, Lancaster T. Antidepressants for smoking cessation. Cochrane Database Syst Rev 2000;4:CD000031.

Wilens TE, Biederman J, Baldessarini RJ, Geller B, Schleifer D, Spencer TJ, Birmajer B, Goldblatt A. Cardiovascular effects of therapeutic doses of tricyclic antidepressants in children and adolescents. J Am Acad Child Adolesc Psychiatry 1996;35(11):1491–501.

OLANZAPINE

OLANZAPINE: THERAPEUTICS

Brands

• Zyprexa

• Olasek

• Ziprexa

• Symbyax (olanzapine-fluoxetine combination)

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)

• Maintaining response in schizophrenia

• Acute agitation associated with schizophrenia (intramuscular)

• Acute mania/mixed mania (monotherapy and adjunct to lithium or valproate) (ages 13 and older)

• Bipolar maintenance

• Acute agitation associated with bipolar I mania (intramuscular)

• Bipolar depression [in combination with fluoxetine (Symbyax)]

• Treatment-resistant depression [in combination with fluoxetine (Symbyax)]

• Other psychotic disorders

• Behavioral disturbances in dementias

• Behavioral disturbances in children and adolescents

• Disorders associated with problems with impulse control

• Borderline personality disorder