Risperidone (Risperdal)

Mechanism of Action: Mechanism of action is believed to be due to antagonism of dopamine (D2) and serotonin (5-HT2) receptors.

Therapeutic Use: Treatment of psychotic disorders.

Absorption: Well absorbed after oral administration. Peak plasma levels are reached in 1 hour.

Metabolism: Metabolized in the liver by cytochrome P450.

Half-life: 3 Hours, but may be as long as 20 hours in a segment of the population that are slow metabolizers .

Average Daily Dose (adult): 4-6 mg

Adverse Effects: Somnolence (sleepiness), headache, dizziness, tremor, dystonia, Parkinsonism, and weight gain.

Drug Interaction: Caution should be used when taken in combination with other centrally acting drugs and alcohol. Because of its potential for inducing hypotension, Risperdal may enhance the hypotensive effects of other therapeutic agents with this potential. Potential interaction with other drugs metabolized by P-450 enzymes.

Contraindication: Contraindicated during lactation. Use with caution in individuals with cardiovascular and cerebrovascular disease.

References:

• Elovic, E. (1996). Atypical antipsychotics: risperidone and clozapine. Journal of Head Trauma Rehabilitation. 11(3), 89-92.
  
• Jean-blanc, W. & Davis, Y. (1995). Risperidone for treating dementia-associated aggression. American Journal of Psychiatry. 152(8), 1239.

Haloperidol (Haldol)

Mechanism of Action: Believed to be due to blockade of dopamine (D2) receptors in the limbic system.

Therapeutic Use: Treatment of psychotic disorders including acute mania, drug-induced sychoses and schizophrenia. Also, for aggressive and agitated clients. Control of tics and vocal utterances of Tourette s Disorder.

Absorption: Peak effect 3-5 hours.

Metabolism: Oxidized by P-450 enzymes.

Half-life: 18-25 hours.

Average Daily Dose (adult): 1-6 mg

Adverse Effects: Extrapyramidal symptoms (involuntary movement). hyperprolactinemia, weight gain, risk of tardive dyskinesia, dry mouth, hypotension.

Drug Interaction: May be capable of potentiating CNS depressants such as anesthetics, opiates and alcohol. Caution should be exercised in patients receiving lithium.

Contraindication: Severe toxic CNS depression or comatose states from any cause and in individuals who are hypersensitive to this drug or have Parkinson s disease. Lactation.

References:

• Wilkinson, R., Meythaler, J. & Guin-Renfroe, S. (1999). Neuroleptic malignant syndrome by haloperidol following traumatic brain injury. Brain Injury. 13(12), 1025.
• 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.

Thioridazine (Mellaril)

Mechanism of Action: Believed to be due to blockade of dopamine (D2) receptors in limbic system.

Therapeutic Use: Treatment of schizophrenia, depression of anxiety, and sleep disturbances.

Absorption: Erratic absorption after oral administration. Time for peak effect: 1-4 hours.

Metabolism: Metabolized in liver by P-450 enzymes.

Half-life: 15-20 hours.

Average Daily Dose (adult): 150-600 mg

Adverse Effects: Drowsiness, dry mouth, blurred vision, urinary retention, orthostatic hypotension.

Drug Interaction: Additive sedative effects with other CNS depressants; potential interaction with other drugs metabolized by P-450 enzymes.

Contraindication: Should not be given to patients with Parkinson s disease or cardiovascular disease.

References:

• Cowen, T.D., & Meythaler, J.M. (1994). Hypotensive effects of thioridazine in an elderly patient with traumatic brain injury.Brain Injury. 8(8), 735.

Chlorpromazine (Thorazine)

Mechanism of Action: Blocks dopamine (D2) receptors in limbic system.

Therapeutic Use: Treatment of psychosis, schizophrenia and acute mania. Can be used to control nausea & vomiting.

Absorption: Erratically absorbed. Peak effect in 2-3 Hours.

Metabolism: Extensive oxidation by P-450 enzymes.

Half-life: 30 Hours.

Average Daily Dose (adult): 300-1000 mg

Adverse Effects: Drowsiness, orthostatic hypotension, dry mouth, blurred vision, xtrapyramidal motor effects (e.g. Parkinsonism, acute dystonia). Danger of tardive dyskinesia.

Drug Interaction: Potential interaction with other drugs metabolized by P-450 system. Additive effect with other CNS depressants.

Contraindication: Do not use in patients with known hypersensitivity to phenothiazines. Do not use in comatose states or in the presence of large amounts of CNS depressants, (Alcohol, barbiturates, narcotics etc).

References:

• Physicians Desk Reference, 1998.
  
• Baldessarini, R. J. In Goodman and Gilman s The Pharmacological Basis of Therapeutics 9th Edition.
• Hardman, J.G. et al. (Eds). McGraw Hill , New York, 1996. pp. 399 - 427.

Fluphenazine (Prolixin)

Mechanism of Action: Blocks dopamine (D2) receptors in the limbic system.

Therapeutic Use: Treatment of psychotic disorders.

Absorption: Well absorbed. Peak plasma level: 1-4 hours.

Metabolism: Oxidized by the P-450 system.

Half-life: 20 hours after oral administration.

Average Daily Dose (adult): 5-10 mg/day

Adverse Effects: High incidence of extrapyramidal symptoms (involuntary movement). Risk of tardive dyskinesia.

Drug Interaction: Additive with other CNS depressants such as benzodiazepines and alcohol. May interact with other drugs that are metabolized by the P-450 enzymes.

Contraindication: Hypersensitivity to phenothiazines. Do not use in comatose states or in the presence of large amounts of CNS depressants.

General References:

Maryniak, O., Manchanda, R. & Velani, A. (2001). Methotrimeprazine in the treatment of agitation in acquired brain injury patients. Brain Injury. 15(2), 167-174.

Perino, C., Rago, R., Cicolin, A., & Torta, R. (2001). Mood and behavioural disorders following traumatic brain injury; clinical evaluation and pharmacological management. Brain Injury. 15(2), 139-148.

Muller, U., Murai, T., Bauer-Wittmund, T. & von Cramon, D. (1999). Paroxetine versus citalopram treatment of pathological crying after brain injury. Brain Injury. 13(10), 805-812.

Azouvi, P., Jokic, C., Attal, N., Denys, P., Markabi, S. & Bussel, B. (1999). Carbamazepine in agitation and aggressive behavior following severe closed-head injury: results of an open trial. Brain Injury. 13(10), 797-804.

Britton, K. (1998). Medroxyprogesterone in the treatment of aggressive hypersexual behavior in traumatic brain injury. Brain Injury. 12(8), 703-708.

Stanislav, S. (1997). Cognitive effects of antipsychotic agents in persons with traumatic brain injury. Brain Injury. 11(5), 335-342.

Zafonte, R. (1997). Treatment of agitation in the acute care setting. Journal of Head Trauma Rehabilitation. 12(2), 78-81.

Bellus, S., Stewart, D., Vergo, J., Kost, P., Grace, J., & Barkstrom, S. (1996). The use of lithium in the treatment of aggressive behaviors with two brain-injured individuals in a state psychiatric hospital. Brain Injury. 10(11), 849-860.

Emory, L.E., Cole, C.M., & Meyer, III, W.J. (1995). Use of Depo-Provera to control sexual aggression in persons with traumatic brain injury.Journal of Head Trauma Rehabilitation. 10(3), 47-58.

Tejera, C. & Saravay, S. (1995). Treatment of organic personality syndrome with low-dose trazodone. Journal of Clinical Psychiatry. 56(8), 374-75.

Boyeson, M.G. & Harmon, R.L. (1994). Acute and postacute drug-induced effects on rate of behavioral recovery after brain injury.Journal of Head Trauma Rehabilitation. 9(3), 78.

Cassidy, J.W. (1994). Neuropharmacological management of destructive behavior after traumatic brain injury.Journal of Head Trauma Rehabilitation. 9(3), 43.

Silver, J.M. & Yudofsky, S.C. (1994). Psychopharmacological approaches to the patient with affective and psychotic features.Journal of Head Trauma Rehabilitation. 9(3), 61.

Silver, J.M. & Yudofsky, S.C. (1993). Pharmacologic treatment of neuropsychiatric disorders.Neurorehabi litation. 3(1), 15-25.

Bakchine, S., Lacomblez, L., Benoit, N., Parisot, D. et al. (1989). Manic-like state after bilateral orbitofrontal and right temporoparietal injury: Efficacy of clonidine. Neurology. 39, 777-781, Jun.

Rose, M.J. (1988). The place of drugs in the management of behavior disorders after traumatic brain injury.Journal of Head Trauma Rehabilitation. 3(3), 7-13.

Glenn, M.B. & Joseph, A.B. (1987. The use of lithium for behavioral and affective disorders after traumatic brain injury.Journal of Head Trauma Rehabilitation. 2(4), 68-76.

Haas, J.F. & Cope, D.N. (1985). Neuropharmacologic management of behavior sequelae in head injury: A case report. Archives of Physical Medicine & Rehabilitation. 66, 472-474, Jul.