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Thioridazine

Thioridazine is a piperidine phenothiazine antipsychotic drug and is used in the treatment of schizophrenia and psychosis. more...

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Thioridazine is a typical low-potency neuroleptic that is slighly less potent than chlorpromazine. It has a halflife of 7 to 13 hours. (Other sources have 16 to 24 hours.) It has the advantage of a low incidence of early and late extrapyramidal side-effects (tardive dyskinesia). In this regard it is very similar to the atypical neuroleptic clozapine (ClozarilĀ®). Thioridazine has also intrinsic mild to moderate antidepressive properties. It has antiemetic properties. Sedation is said to be less pronounced compared with chlorpromazine.

Indications

Previous additional indications were agitated depression, tension and anxiety linked to alcohol withdrawal and dysphoria of epileptic patients. It had even (MellerettenĀ® in Europe) an indication for the treatment of psychosis in children and adolescents (10mg to 60mg daily).

It was also given off-label for the treatment of insomnia and for alleviation of opiate withdrawal.

Thioridazine is known to kill multidrug-resistant mycobacterium tuberculosis and MRSA at clinical concentrations..

Metabolism

Thioridazine is a racemic compound with two enantiomers, both of which are metabolized, according to Eap et al, by CYP2D6 into (S)- and (R)-thioridazine 2-sulfoxide, better known as mesoridazine, and into (S)- and (R)-thioridazine-5-sulfoxide. Mesoridazine is in turn metabolized into sulforidazine. Thioridazine is an inhibitor of CYP1A2 and CYP3A2

Side Effects

Central nervous system side-effects occur. These are mainly drowsiness, dizziness, fatigue, and vertigo. Early and late extrapyramidal side-effects are seen only infrequently (less than 1% altogether). There is no clear dose-effect relationship, as with higher doses anticholinergic effects of thioridazine become more prominent.

Thioridazine causes also an unusual high incidence of impotence and anorgasmia due to a strong alpha-blocking activity. Painful ejaculation or no ejaculation at all is also sometimes seen.

Autonomous side-effects (dry mouth, urination-difficulties, obstipation, induction of glaucoma, postural hypotension, and sinus tachycardia) occur obviously less often than with most other mildly potent antisychotics.

Thioridazine is no longer recommended as first-line treatment due its side-effect of prolonging the QT interval on the EKG. Thioridazine-5-sulfoxide is responsible for the (ventricular tachycardia, torsades de pointes) according to Heath, Svensson and Martensson.

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Sexually inappropriate behaviors: assessment necessitates careful medical and psychological evaluation and sensitivity
From Geriatrics, 1/1/05 by Jary M. Lesser

Primary care physicians who see older patients will likely encounter reports of sexually inappropriate behavior, but may lack training in how to deal with such behaviors. The behaviors in question range from the grossly inappropriate to the fairly subtle, in which observer bias must be considered. Situations involving sexual acting out by an older person are complex, and prompt the following questions:

* Does mildly aberrant behavior represent lifelong eccentricity, or is it caused by impaired judgment and impulse control?

* Are adult children or nursing home directors realistically concerned, or are they biased and hypersensitive to litigation?

* Is a charming, unconventional, and glib octogenarian a "free spirit" or a case of early dementia? (1)

Assessing sexually inappropriate behaviors in community-dwelling and institutionalized older adults requires careful medical and psychological evaluation, as well as sensitivity.

Nursing home residents

Nursing homes with many demented residents, including helpless, confused, and immobilized patients, constitute fertile ground for resident-to-resident sexual abuse. Cognitive impairment, especially among male patients, and patients with frontal and temporal cortical insults, has been associated with an increased risk of sexual impropriety. (2) Demented patients who may be unaware of their surroundings and masturbate in the dayroom, may actually be expressing a need for intimacy of a nonsexual nature, or may misidentify a stranger as their spouse and partner. (3)

Staff and administrators of nursing homes vary in their level of training and awareness of behavioral techniques to assess the sexual behavior of their residents. Funding for training programs and staff-to-resident ratios also varies among nursing facilities.

The goal of care should be a commitment to maintaining the dignity and minimal restriction of residents. In the patient bill of rights, federal regulations mandate a least restrictive environment. (3) Consequently, the medical director of a nursing home is in a peculiar bind because the environment must be simultaneously nonrestrictive and safe. The burden of controlling aberrant behavior then falls on the physician. Ideally, staff members would employ behavioral techniques to redirect impulsive behaviors and avoid excessive medication. In reality, this may be an unrealistic expectation.

Independent living patients

Cases involving persons who live independently are no less complicated, and have the added problem of a great stigma attached to the patient and reflected on family members. These families may benefit from counseling to deal with their feelings of shame and anger.

Assessment

In the older patient, sexually inappropriate behavior is almost always a result of neurologic/cognitive impairment, which may be aggravated by medications, concomitant medical problems, or environmental factors (Table 1).

Dementia and delirium are psychiatric syndromes that must be considered. General medical assessment should include medical and sexual history, review of current medications, mental status examination, and extensive physical and neurologic examinations. Routine laboratory assessments and special tests, including drug screens and testosterone levels as dictated by the patient's presenting circumstances, are recommended.

The most common causes of dementia are Alzheimer's disease and vascular insults.

The diagnosis of dementia is not always simple: a mental status exam will usually reveal deficits in recent memory, orientation, fund of knowledge, calculation, insight, and judgment. In addition, subtle or mild dementias in very bright people can be difficult to recognize. The Folstein Mini-Mental State Examination (4) and the Clock Drawing Test (5) are two simple, well-validated instruments easily administered in the office. Referral to a neuropsychologist for testing will provide detailed and specific data for a more definitive diagnosis that should also include recommendations for approaching behavioral disturbances, such as sexual inhibition. As part of the cognitive assessment, careful observation of the doctor-patient interaction will reinforce the diagnosis of dementia and provide indications of problems with impulse control and social judgment. Impaired patients often exhibit problems with the organization of thinking, impulse control, and empathy. Specifically, patients are verbose and circumstantial, cannot inhibit irrelevancies, and show little sensitivity to the time constraints of the interviewer. These patients often have some level of disinhibition, (1,6,7) as in the following case:

Mr. H is a 75-year-old man who was married for 45 years and has a distant past history of promiscuity. He is a retired accountant and spends his days watching television and playing golf. He is court-ordered to undergo psychiatric evaluation after sexually fondling the 15-year-old daughter of his next door neighbor, with whom he had been ingratiating himself. He appears well-groomed and affable, joking about the incident, and showing little embarrassment. The mental status exam discloses temporal disorientation, impaired short-term memory, poor calculating ability, and concreteness.

Significantly, gross cognitive impairment with disinhibition may go unrecognized on superficial assessment.

Delirium often coexists with dementia and has multiple causes, including medications (particularly benzodiazepines and anticholinergics), acute medical disorders (metabolic, cardiopulmonary, endocrine, infectious), and acute cerebral insult (stroke, head injury, seizure). Diagnosis depends on recognition of a change in mental state with impaired attention and level of consciousness, hallucinations, and agitation. An underlying medical cause must be identified.8

Delirium, like dementia, can also go unrecognized. This is particularly the case for quietly confused patients as opposed to disruptive ones.

Management

Pharmacologic management includes hormonal manipulation and treatment with psychotropic medication. Hormonal agents are used to decrease testosterone levels, which seems to reduce sexual drive. (9, 10) Treatment with estrogens, antiandrogens, gonadotropin-releasing analogs, and methylprogesterone acetate have all shown variable success. Psychotropic medications also provide mixed results in the treatment of hypersexuality; antipsychotics, (11,12) beta blockers, (13) antianxiety agents, (13) antimanic drugs,13,14 cholinesterase inhibitors,15 selective serotonin reuptake inhibitors (SSRIs), (16-18) and benzodiazepines (19,20) have all been tried (Table 2).

Some consistency of success has been seen with SSRIs, as in this case:

Mr. K is an 85-year-old man who lives with his wife of 57 years. For 3 years, he has been having increasing problems with memory and orientation, and has become more impulsive and argumentative. He insists on driving, drinks up to three scotches a day, and lately has been exposing himself to the female housekeeper. His wife reports that the alcohol worsens his behavior. His previous physician medicated him with lorazepam, 0.5 mg tid, with abrupt worsening of his behavioral problems.

A consultation is sought with a geriatric psychiatrist who, after examining the patient and reviewing lab and cerebral MRI reports, confirms a diagnosis of probable Alzheimer's disease, and carefully tapers the lorazepam. The patient has no insight, insisting that he is perfectly capable of caring for himself, of driving, and of drinking as much as he wants. He denies exposing his genitals. He is medicated with risperidone, titrated to 2.5 mg/d. This markedly reduces his behavioral symptoms, but renders him apathetic and depressed. Sertraline, 25 mg/d, is added and the risperidone tapered down and discontinued. Ultimately, his disinhibited behavior essentially disappears while taking the sertraline and donepezil, 10 mg/d. His cognitive exam is unchanged.

Nonpharmacologic interventions include counseling for family members, and various behavioral techniques for institutionalized patients. The effectiveness of the behavioral techniques depends upon an appropriate level of staffing (in the nursing home) and training of caregivers. (21)

Conclusion

Inappropriate sexual behavior in older adults requires careful assessment, and individualized, often multidisciplinary, treatment planning. This might include, to varying degrees, cognitive, behavioral, and pharmacologic interventions. As illustrated by the two cases, underlying cognitive impairment may not be immediately apparent, and may require flexibility in pharmacotherapy. Utilizing an individualized and multidisciplinary approach will ensure greater success in relieving caregiver burden and restoring dignity to the patient.

References

(1.) Burns A, Jacoby R, Levy R. Psychiatric phenomena in Alzheimer's disease. IV: Disorders of behaviour. Br J Psychiatry 1990; 157:86-94.

(2.) Robinson KM. Understanding hypersexuality: A behavioral disorder of dementia. Home Health Nurse 2003; 21(1): 43-7.

(3.) Kamel HK, Hajjar RR. Sexuality in the nursing home, part 2: Managing abnormal behavior--legal and ethical issues. J Am Med Dir Assoc 2003; 4(4):203-6.

(4.) Folstein MF, Folstein SE, McHugh PR. "Mini-mental state:" A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12(3):189-98.

(5.) Gruber NP, Varner RV, Chen YW, Lesser JM. A comparison of the clock drawing test and the Pfeiffer Short Portable Mental Status Questionnaire in a geropsychiatry clinic. Int J Geriatr Psychiatry 1997; 12(5):526-32.

(6.) Burns A, Jacoby R, Levy R. Psychiatric phenomena in Alzheimer's disease. I: Disorders of thought content. Br J Psychiatry 1990; 157:72-6.

(7.) Royall DR, Mahurin RK, Gray KF. Bedside assessment of executive cognitive impairment: The executive interview. J Amer Geriatr Soc 1992; 40(12):1221-6.

(8.) Wells CE. Organic mental syndromes and disorder. In, Comprehensive Textbook of Psychiatry/IV. Edited by Kaplan H, Sadock B. Baltimore: Williams & Wilkins; 1985: 838-51.

(9.) Levitsky AM, Owens NJ. Pharmacologic treatment of hypersexuality and paraphilias in nursing home residents. J Am Geriatr Soc 1999; 47(2):231-4.

(10.) Schiavi RC, White D. Androgens and male sexual function: A review of human studies. J Sex Marital Ther 1976; 2(3):214-28.

(11.) Tariot PN, Profenno LA, Ismail MS. Efficacy of atypical antipsychotics in elderly patients with dementia. J Clin Psychiatry 2004; 65 (Suppl 11):11-5.

(12.) Hoeh N, Gyulai L, Weintraub D, Streim J. Pharmacologic management of psychosis in the elderly: A critical review. J Geriatr Psychiatry Neurol 2003; 16(4):213-8.

(13.) Zannino G, Gargiulo A, Lamenza F, Marotta MG, Barzotti T, Silvestri A, Ettorre E, Marigliano V. The management of psychogeriatric patient. Arch Gerontol Geriatr Suppl 2004; (9):465-70.

(14.) Tariot PN, Erb R, Leibovici A, et al. Carbamazepine treatment of agitation in nursing home patients with dementia: A preliminary study. J Am Geriatr Soc 1994; 42(11):1160-6.

(15.) Rosler M. The efficacy of cholinesterase inhibitors in treating the behavioural symptoms of dementia. Int J Clin Pract Suppl 2002; (127):20-36.

(16.) Lothstein LM, Fogg-Waberski J, Reynolds P. Risk management and treatment of sexual disinhibition in geriatric patients. Conn Med 1997; 61(9):609-18.

(17.) Alkhalil C, Tanvir F, Alkhalil B, Lowenthal DT. Treatment of sexual disinhibition in dementia: Case reports and review of the literature. Am J Ther 2004; 11(3):231-5.

(18.) Simpson DM, Foster D. Improvement in organically disturbed behavior with trazodone treatment. J Clin Psychiatry 1986; 47(4):191-3.

(19.) Patel S, Tariot PN.Pharmacologic models of Alzheimer's disease. Psychiatr Clin North Am 1991; 14(2):287-308.

(20.) Lister RG, File SE.The nature of lorazepam-induced amnesia. Psychopharmacology (Berl) 1984; 83(2):183-7.

(21.) Ehrenfeld M, Tabak N, Bronner G, Bergman R. Ethical dilemmas concerning sexuality of elderly patients suffering from dementia. Int J Nurs Pract 1997; 3(4):255-9.

Jary M. Lesser, MD * Susan V. Hughes, BS * James R. Jemelka, MA * John Griffith, MD

Jary M. Lesser, MD, is associate professor of psychiatry and chief of the Gero-Psychiatry Clinic at the University of Texas Medical School in Houston.

Susan V. Hughes, BS, is research assistant in psychopharmacology, mood disorders in the elderly, and dementia, University of Texas Medical School.

James R. Jemelka, MA, is research assistant, department of Psychiatry, University of Texas Medical School.

John D. Griffith, MD, is clinical assistant professor, University of Texas Medical School. He is an authority on drug toxicity and legal issues in medicine.

Disclosure: The authors have no real or apparent conflicts of interest relating to the subject presented here.

COPYRIGHT 2005 Advanstar Communications, Inc.
COPYRIGHT 2005 Gale Group

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