Psychopharmacology Tips

Clinical observations suggest that patients with a history of benzodiazepine abuse are resistant to the anxiolytic effects of buspirone.

Ref: - Schweizer, E. & Rickels, K. (1986) Failure of buspirone to manage benzodiazepine withdrawal. American Journal of Psychiatry, 143, 1590-1592.

An elevated Blood Urea Nitrogen level can increase toxic potential of various psychotropic medications, especially lithium and amantadine.

Ref: - Rosse, R.B., Deutsch, L.H. & Deutsch, S.I. (2000) Medical assessment and laboratory testing in Psychiatry. In: Comprehensive Textbook of Psychiatry, Vol, 1, Edn. 7, (Eds.) Sadock, B. J. & Sadock, V. A. pp 732-755, Philadelphia: Williams and Wilkins.

Elderly patients or others at increased risk for hypotensive effects may tolerate olanzapine better than risperidone.

Ref: - Madhusoodanan, S., Suresh, P., Brenner, R. & Pillai, R. (1999) Experience with the atypical antipsychotics – risperidone and olanzapine in the elderly. Annals of Clinical Psychiatry, 11, 113-118.

Cases have been reported in which it was helpful to add the anticholinergic antipsychotic thioridazine for a transitory weaning period before eventually switching a patient from clozapine to another new-generation antipsychotic. This would in theory blunt the proposed increase in cholinergic tone precipitated by the removal of clozapine. However, considering the risk of QTc elevation with thioridazine, a safer alternative might be an anticholinergic antiparkinsonian drug.

Ref: - Osser, D.N. & Sigadel, R.S. (2001) Short-term inpatient pharmacotherapy of schizophrenia. Harvard Review of Psychiatry, 9, 89-104.

Prior agranulocytosis caused by standard neuroleptics is not a contraindication to subsequent treatment with clozapine.

References: -
Bauer, M. (1995) Concurrent agranulocytosis and acute hepatitis resulting from combination of classic neuroleptics and subsequent successful clozapine treatment. Pharmacopsychiary, 28, 29-31.

Bauer, M. & Mackert, A. (1994) Clozapine treatment after agranulocytosis induced by classic neuroleptics. Journal of Clinical Psychopharmacology, 4, 71-73.

Clozapine has been reported to reduce smoking in patients with schizophrenia, especially among the heaviest smokers.

Ref: - Albanese, M.J., Khantzian, E.J., Murphy, S.L., et al. (1994) Decreased substance use in chronically psychotic patients treated with clozapine. American Journal of Psychiatry, 152: 780-781.

Reboxetine was found to attenuate olanzapine-induced weight gain in a double-blind study of 26 patients with schizophrenia.

Ref: - Poyurovsky, M., Isaacs, I., Fuchs, C., et al. (2003) Attenuation of olanzapine-induced weight gain with reboxetine in patients with schizophrenia: a double-blind, placebo-controlled study. American Journal of Psychiatry, 160, 297-302.

Though the antimanic effect of lithium occurs within 6-10 days, there is a delay of 6-8 weeks in onset of its antidepressant effect.

References: -

Franchini L., Zanardi, R., Gasperini, M., et al. (1996) Fluvoxamine and lithium in long term treatment of unipolar subjects with high recurrence rate. Journal of Affective Disorders, 38: 67-69.

Zornberg, G.L. & Pope H.G. Jr. (1993) Treatment of depression in bipolar disorder: new directions for research. Journal of Clinical Psychopharmacology, 13: 397-408.

Typical antipsychotics may negatively influence the course of bipolar disorder by inducing (post-mania) depression and rapid cycling

Ref: - Kukupulos, A., Reginaldi, D., Laddomada, P., et al. (1980) Course of the manic-depressive cycle and changes caused by treatment. Pharmakopsychiatrie Neuropsychopharmakol, 13: 156-157.

A useful guiding rule: manic patients are always worse than they appear.

Ref: - Royal Australian and New Zealand College of Psychiatrists Clinical Practice Guidelines Team for Bipolar Disorder. (2004) Australian and New Zealand clinical practice guidelines for the treatment of bipolar disorder. Australian and New Zealand Journal of Psychiatry, 38: 280-305.

Nefazodone undergoes extensive first-pass metabolism, resulting in bioavailability of only 15 – 23%. As is usually the case, first-pass metabolism becomes saturated with chronic dosing, resulting in greater elevations of plasma concentration with dosage increases later in treatment.

Ref: - Dubovsky, S.L. & Thomas, M. (1995) Serotonergic mechanisms and current and future psychiatric practice. Journal of Clinical Psychiatry, 56 (suppl 2): 38-48.

Estrogens in high doses may impair the efficacy of imipramine, whereas low doses may enhance it.

Ref: - Kendall, D.A., Stancel, G.M., Enna, S.J. (1982) The influence of sex hormones on antidepressant-induced alterations in neurotransmitter receptor binding. Journal of Neurosciences, 2: 354-360.

Women appear to have a greater incidence of hypothyroidism secondary to lithium treatment.

Ref: - Goble, F.C. (1975) Sex as a factor in metabolism, toxicity, and efficacy of pharmacodynamic and chemotherapeutic agents. In: Garratini, S., Goldin, A., Hawking, F., et al. (Eds.) Advances in Pharmacology and Chemotherapy. New York NY: Academic Press. 173-252.

This condition typically affects middle aged or older men. No systematic studies of treatment have been performed; but clozapine, propranolol or paroxetine may be effective.

Ref: - Mahowald, M.W. & Schenck, C.H. (2000) REM sleep parasomnia. In: Kryger, M.H., Roth, T. & Dement, W.C. (Eds.) Principles and Practice of Sleep Medicine. Philadelphia: W B Saunders, 724-741.

Risperidone and Quetiapine: Food and smoking do not modify the pharmacokinetics
Olanzapine: Bioavailability unaffected by food; smoking can reduce its half life
Clozapine: Bioavailability not affected by food; half life could be reduced by smoking

Ref: - Tandon, R., Milner, K. & Jibson, M.D. (1999) Antipsychotics from theory to practice: integrating clinical and basic data. Journal of Clinical Psychiatry, 60 (suppl 8): 21-28.

The hallucinations of Charles Bonnet syndrome may be self-limiting and benefit from improved lighting, although some patients may also require antipsychotic medication.

Ref: - Targum, S.D. & Abbott, J.L. (1999) Psychoses in the elderly: a spectrum of disorders. Journal of Clinical Psychiatry, 60 (suppl 8): 4-10.

Patients with late-onset schizophrenia tend to respond to lower doses of antipsychotic medication than patients with early onset schizophrenia.

Ref: - Larco, J.P. & Jeste, D.V. (1997) Geriatric psychosis. Psychiatric Quarterly, 68: 247-260.

Hyperhidrosis (excessive sweating) in patients suffering from social phobia may be controlled by topical application of aluminium chloride in alcohol; while a generalised form of the symptom usually responds to clonidine or terazosin

Ref: - Papp, L.A. (2000) Anxiety disorders: somatic treatment. In: Comprehensive Textbook of Psychiatry, Vol, 1, Edn. 7, (Eds.) Sadock, B. J. & Sadock, V. A. pp 1490-1498, Philadelphia : Williams and Wilkins.

Depressed patients with significant psychomotor retardation often seem to require at least 40 mg/day of fluoxetine.

Ref: - Schatzberg, A.F., Cole, J.O. & DeBattista, C. (2003) Manual of Clinical Psychopharmacology. Washington, DC: American Psychiatric Press.

Jaundice has been noted to occur in 0.1%-0.5% of patients taking chlorpromazine. This usually occurs within the first month after the initiation of treatment and generally requires discontinuation of treatment. Given the relative infrequency of antipsychotic-induced jaundice, other etiologies for jaundice should be evaluated before the cause is judged to be the antipsychotic medication.

Ref: - American Psychiatric Association practice guideline for the treatment of patients with schizophrenia (first edition)

Knowledge of the patient’s personality and defense mechanisms might be useful in planning pharmacotherapy.

For instance, a patient with paranoid personality or paranoid traits may be suspicious about medications as well as the physician’s intentions, and may have a tendency to misinterpret medication side effects.

Patients with an underlying narcissistic pathology may argue with the physician and try to handle the side effects on their own.

A person with comorbid obsessive compulsive personality disorder or obsessive compulsive personality traits will need exact instructions as to how to take medication, including exact dosing times, to feel comfortable. He or she will require very detailed discussions of side effects before the treatment begins. An obsessive-compulsive patient will also be careful to watch for side effects and discuss them in detail during treatment. However, the obsessive-compulsive patient is usually more compliant.

Patients with an underlying borderline pathology may stop the medication abruptly because of any side effects. They may also use the issue of side effects in splitting the treating physician and therapist. Borderline patients may require repeated education about the possible side effects and their management.

Patients with histrionic personality disorder or histrionic traits may mix up exact times and feel guilty, and they may also miss doses when the dosing schedule is too rigorous. A seductive histrionic patient may also try to please the treating physician by minimizing the side effects.

In conclusion, one must consider overt personality pathology in treatment-planning as well as side effects management. One might tailor the instructions and information about the medications and their side effects to a patient's underlying personality pathology.

Ref: - Balon, R. (1998) General issues in the management of side effects of psychotropic drugs. In: (Ed) Balon, R., Practical management of the side effects of psychotropic drugs. pp 1- 16, New York: Basel.

If a patient receiving an antipsychotic experiences a seizure, the antipsychotic (with the exception of clozapine) should be withdrawn or the dose reduced by 50% until a neurologic evaluation is completed.

Ref: - American Psychiatric Association practice guideline for the treatment of patients with schizophrenia (first edition)

Many patients suffering from affective disorders may intermittently experience symptoms during the continuation phase of their treatment, and this phenomenon has been called “roughening”. Roughening with features of depression often resolves without intervention. However, roughening with symptoms of mood elevation in bipolar patients should be monitored more closely, because this type of symptom recurrence appears more likely to develop into a full affective episode.

Ref: - Rosenbaum, J.F., Fava, M., Nierenberg, A.A. & Sachs, G.S. (1999) Treatment-resistant mood disorders. In: Treatment of Psychiatric Disorders. (Ed) Gabbard, G.O. pp 1275 – 1328. New Delhi: Jaypee Brothers

Gender is emerging as an important factor in tolerability and efficacy of a given antidepressant class. Substantial evidence suggests that men may respond to and tolerate the TCAs better than do women. Conversely, women appear to do better with serotonergic agents than do men.

Ref: - Schatzberg, A.F., Cole, J.O. & DeBattista, C. (2003) Manual of Clinical Psychopharmacology. Washington, DC: American Psychiatric Press.

If depression is associated with the prodrome or onset of a psychotic episode, antipsychotic medication is usually the most effective treatment for both the depression and the psychotic episode. However, when depression occurs in the context of relative remission of psychosis, antidepressant medication can be useful.

Ref: - Siris, S.G., Morgan, V., Fagerstrom, R., et al. (1987) Adjunctive imipramine in the treatment of postpsychotic depression: a controlled trial. Archives of General Psychiatry, 44: 533-539.

In contrast to lithium, there are no reports of carbamazepine discontinuation induced refractoriness. In fact, tolerance and loss of efficacy, which is associated with long-term use of anticonvulsants, may be decreased with a period of time off the medication with subsequent reresponse with rechallenge.

Ref: - Pazzaglia, P.J. & Post, R.M. (1992) Contingent tolerance and reresponse to carbamazepine: a case study in a patient with trigeminal neuralgia and bipolar disorder. Journal of Neuropsychiatry and Clinical Neurosciences, 4, 76 – 81.

Placebo response rates in patients with recent onset of a first depressive episode of moderate severity have been reported to be as high as 70%. Patients who relapse following an apparent initial antidepressant response may do so because of a loss of the placebo effect.

Ref: - Potter, Z. & Schmidt, M.E. (1997) Treatment of major depression: selection of initial drug. In: Mood disorders: systematic medication management. (Ed) Rush, A.J., Basel: Karger.

American Psychiatric Association practice guideline for the treatment of patients with schizophrenia (Second Edition, 2004) suggests checking ECG and serum potassium levels before starting treatment with thioridazine, mesoridazine, or pimozide; due to risk of QTc prolongation.

Risk factors for mood destabilization with antidepressants in bipolar disorder:

• Genetic risk factors
• Early age at illness onset
• Comorbid substance abuse/dependence
• A h/o rapid cycling
• Multiple antidepressant trials
• H/o antidepressant-induced manias

Assessing for these risk factors before antidepressants are used in bipolar patients may help to reduce the risk for adverse consequences.

Ref: - Goldberg, J.F. (2003) When do antidepressants worsen the course of bipolar disorder? Journal of Psychiatric Practice, 9, 181-194.

In patients of bipolar depression, avoid abrupt cessation of antidepressants to minimize withdrawal or rebound inductions of mania.

Ref: - Goldstein, TR, et al. (1999) antidepressant discontinuation-related mania: critical prospective observation and theoretical implications in bipolar disorder. Journal of Clinical Psychiatry, 60, 563-567.

The response a depressed patient is showing while on an antidepressant may not be due to the effects of the drug. Response occurring while the patient is on a very low dose, developing very early after treatment commencement, or closely related in timing and context to reversal of a major stress is strongly suggestive of a non-pharmacological response, and continuation therapy with the antidepressant may not be needed in these situations.

Ref: - Paykel, E.S. & Scott, J. (2000) Treatment of mood disorders. In: New Oxford Textbook of Psychiatry (Eds) Gelder, M. G., López-Ibor Jr, J. J. & Andreasen, N., Oxford: Oxford University Press.