Amitriptyline (Elavil)
Mechanism of Action: One of a group of tricyclic antidepressants whose action is believed to be related to its ability to block the reuptake of serotonin and norepinephrine which prolongs the action of these neurotransmitters. The exact mechanism of action is not known.
Therapeutic Use: Depression and depression with anxiety and insomnia (disturbed sleep patterns). Also used with chronic pain due to cancer and other pain syndromes, including cluster and migraine headaches. Has been investigated for use with emotional lability (pathological laughing and crying) due to brain damage. Antidepressant effects may require 3 weeks before any benefit is observed.
Absorption: Fairly well absorbed after oral administration. Peak blood levels are reached in 2-8 hours.
Metabolism: Metabolized by N-demethylation and hydroxylation by P-450 enzymes. The hydroxylated form is conjugated. Virtually the entire dose is excreted as glucuronide or sulfate conjugate of metabolites, with little unchanged drug appearing in the urine.
Half-life: 31-46 hours.
Average Daily Dose (adult): 75-150 mg
Adverse Effects: Drowsiness, dry mouth, blurred vision, urinary retention, constipation, dizziness, cardiac palpitations or other arrhythmias,. High doses may cause seizures.
Drug Interaction: It should not be given concomitantly with monoamine oxidase inhibitors.
Contraindication: Sensitivity to the drug. Used with caution in patients with a history of seizures, urinary retention, angle-closure glaucoma or increased intraocular pressure.
References:
- Szlabowicz, J.W. & Stewart, J.T. (1990). Amitriptyline treatment of agitation associated with anoxic encephalopathy. Archives of Physical Medicine & Rehabilitation. 71, 612-613, Jul.
- Jackson, R.D., Corrigan, J.D. & Arnett, J.A. (1985). Amitriptyline for agitation in head injury. Archives of Physical Medicine & Rehabilitation. 66, 180-181, Mar.
Rao, N., Jellinek, H.M. & Woolston, D.C. (1985). Agitation in closed head injury: Haloperidol effects on rehabilitation outcome. Archives of Physical Medicine & Rehabilitation. 66, 30-34, Jan.
Nortriptyline (Pamelor)
Mechanism of Action: Another tricyclic antidepressant whose action is similar to amitriptyline, but fairly selective inhibitor of norepinephrine reuptake.
Therapeutic Use: Treatment of depression and chronic neurogenic (nerve tissue ) pain.
Absorption: Fairly well absorbed, peak plasma level in 2-6 hours.
Metabolism: Liver P-450 enzymes; oxidized metabolites excreted as conjugates.
Half-life: 18-44 hours.
Average Daily Dose (adult): 75-150 mg.
Adverse Effects: Hypotension, tachycardia, confusional states (especially in the elderly), numbness, tingling, dry mouth, skin rash, nausea and vomiting.
Drug Interaction: Dangerous reaction can occur if combined with monoamine oxidase inhibitors.
Contraindication: Monoamine oxidase inhibitors. Hypersensitivity to the drug. Contraindicated during the acute recovery period after myocardial infarction.
Desipramine (Norpramine)
Mechanism of Action: A tricyclic antidepressant similar to nortriptyline. Action believed to be related to blockade of norepinephrine reuptake. Thus, it prolongs the action of this neurotransmitter.
Therapeutic Use: Depression
Absorption: Fairly well absorbed. Peak plasma concentration reached in 2-6 hours.
Metabolism: Rapidly absorbed from the gastrointestinal tract. Metabolized in the liver, and approximately 70% is excreted in the urine.
Half-life: 20-25 hours.
Average Daily Dose (adult): 125-300 ng/ml 100-200 mg/day.
Adverse Effects: Hypotension, hypertension, confusional states, numbness, tingling, dry mouth, skin rash.
Drug Interaction: MAO-inhibitors.
Contraindication: Should not be given in conjunction with, or within 2 weeks of, treatment with an MAO inhibitor drug; hyperpyretic crises, or severe convulsions.
.
Fluoxetine (Prozac)
Mechanism of Action: Fluoxetine is one of the selective serotonin reuptake inhibitors (SSRIs). Its beneficial effects are believed to be related to this effect.
Therapeutic Use: Depression; obsessive compulsive disorders; and bulimia.
Absorption: Well absorbed from GI tract independent of presence of food. Peak plasma levels observed after 6 to 8 hours.
Metabolism: Extensively in the liver, by P-450 enzymes; active metabolite. Has a long half-life.
Half-life: 7-9 days.
Average Daily Dose (adult): 20-40 mg
Adverse Effects: Insomnia, (disturbed sleep patterns), anxiety, nervousness, dizziness, fatigue, gastrointestinal disturbance, nausea.
Drug Interaction: Should not be used with MAO inhibitors; prolongs the half-life and increases blood levels of other drugs metabolized by P-450 enzymes such as benzodiazepines.
Contraindication: Known hypersensitivity to the drug, and MAO inhibitors are contraindicated.
References:
- Patterson, D., Braverman, S., & Belandres, P. (1997). Speech dysfunction due to trazodone-fluoxetine combination in traumatic brain injury. Brain Injury. 11(4), 287-292.
- Barondes, S.H. (1994). Thinking about Prozac. Science. 263, 1102, Feb 25.
- Seliger, G.M., Hornstein, A., Flax, J., Herbert, J. et al (1992). Fluoxetine improves emotional incontinence.Brain Injury. 6(3), 267-270.
- Sloan, R.L., Brown, K.W. & Pentland, B. (1992). Fluoxetine as a treatment for emotional lability after brain injury.Brain Injury. 6(4), 315-319.
Clomipramine (Anafranil)
Mechanism of Action: A tricyclic antidepressant that primarily inhibits serotonin reuptake.
Therapeutic Use: Treatment of obsessive-compulsive disorder that causes distress and interferes with social and vocational activities.
Absorption: Fairly well absorbed; reaches peak plasma levels in 2-6 hours after oral administration.
Metabolism: Clomipramine is extensively biotransformed to desipramine and other metabolites by the P-450 enzymes. The metabolites are excreted as glucuronide conjugates. These metabolites are excreted in urine and feces.
Half-life: 19-37 hours
Average Daily Dose (adult): 100-200 mg.
Adverse Effects: Drowsiness, tremor, dizziness, headache, dry mouth, constipation and weight gain.
Drug Interaction: The risks of using Anafranil in combination with other drugs have not been systematically evaluated. Given the primary CNS effects, caution is advised in using it concomitantly with other CNS-active drugs.
Contraindication: Hypersensitivity to Anafranil or other tricyclic antidepressants. Should not be given in combination or within 14 days before or after treatment with a MAO inhibitor.
References:
- Leo, R. & Kim, K. (1995). Clomipramine (Anafranil) treatment reduces sexually inappropriate behavior in two elderly men w/dementia. Brain Injury Update. 10(8), 59.
Sertraline (Zoloft)
Mechanism of Action: Inhibits neuronal uptake of serotonin. In this regard it is classified as a selective serotonin reuptake inhibitor (SSRI).
Therapeutic Use: Treatment of depression, obsessive-compulsive disorders and panic disorders.
Absorption: Fairly well absorbed. Peak plasma level reached 4-8 h after a single dose.
Metabolism: The principle initial pathway of metabolism for sertraline is N-demethylation by P-450 system.
Half-life: 26 hours
Average Daily Dose (adult): 100-150 mg
Adverse Effects: Headache, insomnia (disturbed sleep patterns), agitation, anxiety, dizziness, nausea.
Drug Interaction: Potential effects of coadministration of drugs highly metabolized by P-450 enzymes.
Contraindication: Concomitant use in patients taking monoamine oxidase inhibitors.
References:
- Mukand, J., Kaplan, M., Senno, R., & Bishop, D. (1996). Pathological crying and laughing: treatment with sertraline. Archives of Physical Medicine and Rehabilitation. 77(12), 1309-1311.
- Benedek, D. & Peterson, K. (1995). Sertraline (Zoloft) eliminates crying spells after stroke. Brain Injury Update. 10(8), 60.
- Buck, O. (1995). Sertralien (Zoloft) reduces violent behavior. Brain Injury Update. 10(8), 60.
Venlafaxine (Effexor)
Mechanism of Action: The mechanism of the antidepressant action of venlafaxine in humans is believed to be associated with its ability to inhibit neuronal serotonin and norepinephrine reuptake and its weak inhibition of dopamine reuptake.
Therapeutic Use: Treatment of depression.
Absorption: Well absorbed. Food has no significant effect on absorption.
Metabolism: Extensively metabolized in the liver by o-demethylation (P-450 enzymes). The o-desmethyl metabolite is active but is conjugated with glucuronic acid and excreted.
Half-life: 5 Hours.
Average Daily Dose (adult): 75-150 mg
Adverse Effects: Anxiety, insomnia (disturbed sleep patterns), anorexia, and sweating.
Drug Interaction: Potential interactions with drugs metabolized by P-450 enzymes, e.g. diazepam, cimetidine, alcohol and haloperidol.
Contraindication: Contraindicated in patients sensitive to the drug. Concomitant use in patients taking MAOIs is contraindicated.
Newburn, G., Edwards, R., Thomas, H., Collier, J., Fox, K. & Collins, C. (1999). Moclobemide in the treatment of major depressive disorder (DSM-3) following traumatic brain injury. Brain Injury, 13(8), 637-642.
Reinhard, D., Whyte, J., Sandel, E. (1996). Improved arousal and inititation following tricyclic antidepressant use in severe brain injury. Archives of Physical Medicine and Rehabilitation. 77(1), 80-83.
Joseph, A.B. & Wroblewski, B. (1995). Depression, antidepressants, and traumatic brain injury.Journal of Head Trauma Rehabilitation. 10(2), 90-95.
Herman, C.D. (1991). Abstract: The incidence of seizures during tricyclic antidepressant drug treatment in a brain-injured population.Journal of Head Trauma Rehabilitation. 6(4), 67-68.
Saran, A. (1988). Antidepressants not effective in headache associated with minor closed head injury. International Journal of Psychiatry in Medicine. 18(1), 75-83.
Anti-Depressants
