Primary Psychiatry. 2003;10(8):60-65
Primary Psychiatry. 2003;10(8):60-65
Primary Psychiatry. 2008;10(7):45-48
Dr. Chemali is director of the Neuropsychiatry Brigham Behavioral Neurology Group Memory Disorders Unit at Brigham and Women’s Hospital, Harvard Medical School, in Boston, Massachusetts.
Disclosure: The author reports no financial, academic, or other support for this work.
Please direct all correspondence to: Zeina Chemali, MD, Brigham and Women’s Hospital, Harvard Medical School, 221 Longwood Ave, Boston, MA 02115; Tel: 617-732-8060; Fax: 617-738-9122; E-mail: email@example.com
• This report of two case studies in elderly women represents the first published incidence of increased libido and hypersexuality associated with donepezil.
• Physicians should be aware of the possibility of this side effect, which was distressing to the elderly patients in the presented cases.
• A possible neurochemical mechanism of action of cholinesterase inhibitors leading to increased sexual arousal is presented.
Can donepezil affect the sexual response in the elderly population? Donezepil, an acetylcholine inhibitor, is commonly used in neuropsychiatry for the treatment of cognitive decline and dementia. This report addresses two elderly female patients who had an increase in their libido and experienced hypersexuality after starting donepezil treatment. Potential explanations for this previously unreported association are discussed.
Donepezil (Aricept) is a centrally active, selective piperidine acetylcholinesterase (AchE) inhibitor with no effect on butyrylcholinesterase (BuChE). Its action on AchE inhibition is reversible.1 The drug is given orally in the dose of 5–10 mg OD. Donepezil exhibits linear pharmacokinetics and reaches its peak plasma level within 3–4 hours after ingestion of the drug. It is metabolized in the liver via cytochrome P450 (CYP) and is preferentially excreted by the kidneys. The half-life of donepezil is 60 hours but can extend up to 100 hours in elderly subjects.
Donepezil is relatively well tolerated. Predominant adverse effects are nausea, vomiting, diarrhea, muscle cramps, insomnia, fatigue, and anorexia. Neurological side effects include dizziness, vertigo, ataxia, restlessness, paresthesia, tremor, seizures, drowsiness, extrapyramidal symptoms, and abnormal crying.2 The causes of these signs are unclear, although they are usually attributed to the drug’s direct cholinergic effects. A few cases of behavioral changes have been reported with donepezil.3-5 They include, but are not limited to, delirium, delusions, irritability, aggression, nervousness, paranoia, and abnormal dreams.
There is no report on the effect of donepezil on sexuality. This report describes two cases of increased libido and hypersexuality experienced by female patients 10 days after starting donepezil treatment targeting their cognitive symptoms.
Mrs. N, an 81-year-old right-handed woman, complained of cognitive changes that had been occurring over the last 3 years. Symptoms involved forgetfulness of names and dates of events, as well as word-finding difficulties. These symptoms later progressed to difficulty following conversations and balancing her checkbook. She also had a history of depression and anxiety treated with fluoxetine. She stopped taking fluoxetine a few months later, as she believed it exacerbated her cognitive symptoms. Later, she was placed on a lower dose of the drug without much success. It was then stopped. Her work-up lead to the diagnosis of mild mixed dementia. She was placed on donepezil 5 mg QOD, which was later increased to 5 mg/day. Her other medications included warfarin sodium crystalline, diltiazem, alendronate sodium, levothyroxine, simvastatin, and a multivitamin.
She noticed an increase in her sexual libido 1 week after beginning the regular dose of donepezil 5 mg/day. She described the feeling as overwhelming. She described obsessive sexual thoughts and the urge to have sex many times during the day. She felt very embarrassed and asked to stop donepezil. An attempt to decrease the donepezil dose to alleviate the symptoms while continuing the medication, was unsuccessful. She stopped taking donepezil and her symptoms abated a few days later. At 6-month follow-up, she noted that she had no recurrence of these symptoms since she stopped taking the drug.
Mrs. M is a 72-year-old right handed woman who had once had a motor vehicle accident. Subsequent to her accident, she had complained of short-term memory loss and word-finding difficulties. She was diagnosed with mild cognitive impairment of the amnestic type. In addition, she suffered from depression and was on citalopram 20 mg/day when she started donepezil 5 mg QOD which was increased to 5 mg/day. Mrs. M became restless, had pressured speech, and complained of increased libido and obsessive sexual thoughts 1 week after she started donepezil. A hypomanic state was diagnosed and her citalopram was tapered off and stopped. Her agitation and pressured speech abated but she continued to complain of the same sexual distressing thoughts leading to frequent masturbation. These thoughts and actions were intolerable to her. She stopped taking donepezil. The symptoms of sexual hyperactivation, increased libido, and compulsive masturbation abated a few days later. At a 3-month follow-up she was found to be moderately depressed, but no other complaints were made. She was treated with bupropion. A year later, the depression was in remission with no recurrence of the unwanted sexual behaviors.
Donepezil is considered to be an essential drug in the treatment of dementia. Its action is due to acetylcholinesterase inhibition and the increase of acetylcholine available to neurons. Donepezil’s affect on sexuality has not been described. One may advance that it is due to the direct cholinergic effect on sexual end organ as the parasympathetic postganglionic neurons and their neurotransmitter acetylcholine are stimulatory to the genitourinary system. This stimulation leads to bladder contraction and increases sexual arousal causing vasodilatation of blood vessels and an increase in blood flow to the sexual organs.
In addition, acetylcholine as a central neurotransmitter is involved in sexual arousal along with nitrous oxide. This type of arousal follows the stage of libido activation and prepares the genitalia for penetration and intercourse. The message of arousal starts in the brain and is relayed in the spinal cord to sympathetic and parasympathetic nerve fibers, vascular tissue, and genitalia.
Previous reports by Kawashima and Yamada3 noted delirium and increased diurnal and nocturnal activation after the use of donepezil. In addition, Wengel and colleagues4 described behavioral complications associated with donepezil, while another report described violent behavior associated with donepezil.5
It is worth noting that both women presented in these cases had a history of depression and were treated with selective serotonin reuptake inhibitors (SSRIs). In case 2, competition for CYP with the addition of donepezil may have triggered a hypomanic state with hypersexuality, gregariousness, and disinhibition by raising SSRI levels. While the rest of the hypomanic symptoms abated when the patient stopped the SSRI, the hypersexuality did not abate until she stopped donepezil.
The two women were very disturbed by their behaviors and found it to be distressing and unacceptable. Decreasing the dose did not make any difference and the behavior abated only when the medication was completely stopped. No subsequent sexual problems were noted at follow-up visits.
Two cases of donepezil treatment associated with side effects of increase libido and hypersexuality were presented. Because of the high frequency use of donepezil and the special elderly population it targets, physicians should be cognizant of this possible side effect along with or in the absence of major mental status changes. In addition, when donepezil is added to other agents, pharmacokinetics and drug interaction must be considered. Further research in this area is needed. PP
1. Stahl S. Essential Psychopharmacology. Neuroscientific Basis and Practical Applications. 2nd ed. New York, NY: Cambridge University Press: 2000:479-489.
2. Physicians Desk Reference. Montvale, NJ: Medical Economics Company, Inc.; 2002:2469-2473.
3. Kawashima T, Yamada S. Delirium caused by donepezil. J Clin Psychiatry. 2002;63:250-251.
4. Wengel SP, Roccaforte WH, Burke WJ, Bayer BL, McNeilly DP, Knop D. Behavioral complications associated with donepezil. Am J Psychiatry. 1998;155:1632-1633.
5. Bouman WP, Pinner G. Violent behavior associated with donepezil. Am J Psychiatry. 1998;155:1626-1627.
Primary Psychiatry. 2008;10(7):65-72
Primary Psychiatry. 2003;10(7):80-96
Dr. Michel is clinical assistant professor in the Department of Psychiatry and Neurology at the Tulane University School of Medicine in New Orleans, Louisianna.
Dr. Willard is professor in the Departments of Psychiatry, and Neurology and Pediatrics at the Tulane University School of Medicine.
Disclosure: The authors report no financial, academic, or other support of this work.
Please direct all correspondence to: Deborah M. Michel, PhD, 824 Amethyst St, New Orleans, LA 70124; Tel: 504-282-7191; Fax: 504-282-7196; E-mail: firstname.lastname@example.org
• The role that family dynamics can potentially play in the development and maintenance of eating disorders is delineated.
• Areas of inquiry for the assessment of family dynamics are presented.
• The importance of family therapy in multidisciplinary treatment of eating disorders is discussed and a brief literature review of support for family treatment of eating disorders is provided.
• Common issues that arise during the course of family treatment of eating disorders are outlined.
How is family treatment of eating disorders conducted and when is it warranted? This article briefly reviews the important role family dynamics can play in the development and maintenance of eating disorders and summarizes support for family treatment of eating disorders. The review presents areas for inquiry in the assessment of family dynamics and discusses the role of family therapy in multidisciplinary treatment. Common issues that arise in the course of therapy are also delineated.
The family dynamics of those with eating disorders, particularly anorexia, have been of interest to clinicians since the disorders were first described1,2 and well past the time that they were recognized as psychological problems.3 In particular, practitioners have noted the association between eating disorders and difficulty with individuation and separation from the family of origin. Peer relationships are vitally important during the developmental stage that occurs between childhood, during which family is the main source of support, and adulthood, when nonfamilial resources become paramount. During adolescence, it is imperative for friends to become of primary interest and for the family to recede to secondary status. If this phenomenon does not occur, the adolescent’s development of normal peer relationships may be inhibited, thus depriving the youngster of appropriate “growing up” experiences. Without a peer group, it is next to impossible to make the necessary transition from the family to the larger world.
The notion that dysfunctional family characteristics play a part in the development of eating disorders is controversial, as some clinicians believe that the observed family problems are a result rather than the cause of the stress associated with having a child with such a frightening illness.4 There is mounting evidence that genetics contribute to the development of eating disorders, although it is commonly believed that an interaction occurs between genetics and environmental stressors that spawns these disorders.5 What we do know is that the family represents the holding environment for the child and it is always necessary to look at which aspects of the family might relate to the occurrence and maintenance of the disease while remembering that it is never useful or appropriate to blame family members for the disease.3
The ways in which family dynamics may contribute to the development of an eating disorder vary. For example, the family may provide an atmosphere which hinders a youngster from establishing an identity, practicing effective communication skills, and/or learning adaptive coping strategies. Furthermore, within the context of the family, an eating disorder may help an adolescent establish a distinct and separate identity from the family, cope with stressors, distract from negative feelings, or provide what she or he considers to be a means of “safe” self expression in an environment that does not allow open self expression.3
We have noted6 that there have been many clinical accounts of the effectiveness of family therapy in the treatment of eating disorders, yet relatively few controlled studies. However, these few studies clearly show that family therapy is an effective modality for treating eating disorders, particularly in adolescents with anorexia. Investigations with families of bulimics also support the use of family treatment, although fewer studies have been conducted with this population compared to families of anorexics. Taken together, research and clinical experience has convinced us that family therapy is a critical part of treatment within a multidisciplinary team approach, and the need for family therapy from a biopsychosocial stance is now widely accepted.4 A more critical overview of the literature in this area is available in Eating Disorders.6
The family therapy process begins with an assessment and is a continuous process throughout treatment.6,7 The assessment involves an evaluation of individual family members as well as the family unit as an interrelated system. Thus, the evaluation will necessarily include all family members living within the home. Other extended family members may also be asked to take part in the assessment if they have a significant relationship with the identified patient. The goal of the assessment is to determine if the familial environment played a role in the development and maintenance of the eating disorder and, if so, to identify the extent to which any problematic issues remain.8 The assessment also addresses how the eating disorder functions within the family system. During the evaluation, it is important to identify: (A) how the symptoms stabilize the family; (B) what role the family plays in stabilizing the symptoms; (C) around what themes the problem is organized; (D) what consequences will follow familial change; and (E) the therapeutic problem or dilemma.7
When conducting the evaluation, the practitioner should begin by obtaining standard psychosocial information for each family member including demographic data, current and previous living arrangements, psychiatric history, medical history, educational and occupational history, social history, and trauma history.6 It is also important to inquire about significant family events as well as family traditions. Gathering background information on each parent’s family of origin will promote identification of multigenerational patterns of relating and behaving.
As recommended by Anderson,9 there is a need to investigate other areas as well.6 First, interactional patterns should be evaluated including marital satisfaction, extent of spousal agreement on parenting, family satisfaction and companionship, patterns of communication, and the overall affective atmosphere of the family. Second, it is important to assess degree of flexibility in allowing family members to alter communication patterns and roles in response to situations and stressors. Third, clinicians should evaluate how sensitive family members are toward one another. Are they hypersensitive and overreactive, uninvolved and insensitive, or somewhere in between? Furthermore, it is suggested that supports and stresses be evaluated. More specifically, degree of support, or lack thereof, that family members afford one another should be assessed in addition to any significant sources of strengths and stressors both within and outside of the family.
Practitioners must also assess the age-appropriateness of rules and responsibilities that are assigned to family members, especially children and adolescents. Lastly, family knowledge of the eating disorder is a critical area of inquiry in terms of etiology, treatment, and recovery in addition to thoughts, feelings, and behaviors associated with it. Family attitudes and behaviors that may impede recovery need to be identified and resolved quickly,8 particularly preoccupations with weight and appearance which may undermine the identified patient’s efforts at recovery.10 Relatedly, it is important to obtain a family history of dieting, exercise, and eating disorders.3
To assist clinicians in family assessment, standardized, self-report measures are available such as the Family Adaptation and Cohesion Evaluation Scale11 and the Family Assessment Measure.12 These instruments examine the quality of familial relationships and familial interactions from an individual family members’ perspective.6 Although these instruments are subject to self-reporting bias, they can nevertheless be helpful secondary sources of information.
As we have written previously,6 recognition of the complexity of eating disorders, combined with the realization that no single healthcare professional can provide comprehensive care for these patients, led to the evolution of a multidisciplinary team approach.3 Family therapy is one arm of this approach. It is based on the tenet that the family is a system, or a group of interconnected parts which affect one another in a stable manner.13 Consequently, the psychotherapeutic focus is on the family system as a whole, instead of any individual member.6 We have stated3 that the family is the context out of which an eating disorder typically arises, and accordingly, necessitates change if an adolescent is to overcome the eating disorder in that environment. As a result, family therapy is often geared toward understanding the role that the identified patient has characteristically played within the family system and how he or she has contributed to maintaining whatever homeostasis has been achieved.
Homeostasis refers to the balance that occurs when all family members adhere to their given, often unspoken, rules of behavior. These rules can be quite rigid, thereby preventing family members from learning more adaptive, flexible coping mechanisms in response to life stressors. In some cases, patients do well in treatment without family participation, especially if the family exhibits a high degree of negative expressed emotion.14 Older patients who do not live with their families of origin may not need family therapy unless it is determined that the family continues to be a stimulating factor in the illness. These patients may be in family therapy with their spouses and children. When a patient still lives with her family, however, family therapy is usually recommended. Marital therapy may be suggested as an adjunctive treatment for those with spouses.3
Family therapy may evolve into marital therapy for the parents of the identified patient or individual therapy for one or both parents. In other cases, these psychotherapies may be recommended as adjunctive treatments. Furthermore, it is not unusual for one of the parents to be referred for individual therapy at the outset of treatment if it is clear that the primary family problem lies within that particular parent-child relationship.3
We have reported6 that family therapy conducted in conjunction with individual psychotherapy greatly improves prognosis10 and is recommended in the Practice Guideline for the Treatment of Patients with Eating Disorders.15 For theoretical or practical reasons, some practitioners treat both the identified patient and the family. We prefer a model using separate therapists for individual and family therapy on the following grounds3: (A) facilitation of the individuation-separation process; (B) less complicated management of confidentiality issues; and (C) division of therapeutic responsibilities.16 This model also addresses any family dysfunction on both an individual level, where it has been introjected, as well as on the present family level.17 Finally, there are some schools of family therapy that advocate parental control over the child’s eating and a professional, family-based treatment manual is available outlining one such method.6,18 It has been noted, however, that most clinicians do not follow this approach.19 In our experience, having a registered dietician (nutritional counselor) with expertise in eating disorders handle all food issues has been most beneficial. In this manner, the family and identified patient can relinquish battles surrounding food, strengthen familial relationships, and focus on relevant psychotherapeutic issues.6
At times, families may present obstacles to the assessment and treatment process.20 Potential difficulties include denial of a problem, minimization of the eating disorder, and/or denial of the psychological origins of the illness. Treatment resistance and lack of familial motivation to change may also be present. Family refusal to participate in treatment and/or to cooperate with treatment recommendations can have a devastating effect on the course of the illness and the potential for recovery.3 When family members refuse to take part in recommended treatment, the patient often feels that he/she alone is the one with “the problem” and is in some way defective. The aforementioned challenges must be confronted and resolved early in treatment so that a therapeutic alliance can be established, thereby enhancing the probability of a successful outcome.20
In response to familial disagreement with some aspect of treatment or treatment recommendations, the family therapist, and possibly the entire treatment team if appropriate, should meet with the family to work out those differences.3 Dealing with such problems in this manner models adaptive coping skills for the entire family and creates an atmosphere of mutual cooperation and respect in which healing can take place.
Although each case of an eating disorder develops for a variety of individualized reasons, that there are issues commonly encountered in family therapy.3,6 One such issue is difficulty with communication. This problem may be characterized by miscommunication, lack of communication, mixed or double messages, or failure to allow overt expression of feelings, either directly or indirectly. Another typical theme involves problems with the separation-individuation process and difficulties that the family has in allowing the child to become independent. Lack of appropriate parent-child boundaries (eg, failure to respect privacy), enmeshment (emotional overinvolvement), or disengagement (emotional distance), are also frequently seen. As mentioned earlier, the roles that family members play which contribute to the development and maintenance of the eating disorder must also be addressed. For example, a sick child might be the mediator between parents in a strained marriage. In addition, the family often has unrealistic expectations of individual members, such as the “superstar child.” Finally, issues of power and control within the family are likely to surface. For more detailed information on family therapy in the treatment of eating disorders, see the list of suggested readings.
Family therapy is an effective modality of treatment for eating disorders, particularly when used in conjunction with individual psychotherapy and nutritional counseling as part of multidisciplinary treatment. For younger patients still living with their families of origin, it is usually essential for recovery and requires the participation of all family members. If the family is highly defensive and critical, parent counseling or family therapy without the identified patient may be recommended. For older patients, family therapy may not be necessary unless the family is thought to play a role in the maintenance of the illness.
A careful and continuous assessment of family dynamics is warranted in order to ascertain the therapeutic needs of the family and to implement appropriate interventions. Family therapy can then be expected to surround common themes while also addressing individualized family concerns. At times, families may present challenges to the assessment and treatment process. These difficulties must be identified, addressed, and resolved early in treatment in order to increase the potential for a successful outcome. PP
1. Gull WW. Anorexia nervosa (apepsia hysterica, anorexia hysterica). Transactions of the Clinical Society of London. 1874;7:22-28.
2. Lasegue C. De l’anorexie hysterique. Archives Generales de Medecine. 1873;1:384-403. French
3. Michel DM, Willard SG. When Dieting Becomes Dangerous: A Guide to Understanding and Treating Anorexia and Bulimia. New Haven, CT: Yale University Press; 2003.
4. Lemmon CR, Josephson, AM. Family therapy for eating disorders. Child Adolesc Psychiatr Clin N Am. 2001;10:519-542.
5. Klump K. A genetic link to anorexia. In: DeAngelis T, ed. Monitor on Psychology. 2002;33:34-36.
6. Michel DM, Willard SG. Family evaluation and therapy in anorexia nervosa, bulimia nervosa, and binge eating disorder. In: Brewerton TD, ed. Eating Disorders. New York, NY: Marcel Dekker. In Press.
7. Vanderlinden J, Vandereycken W. Family therapy within the psychiatric hospital: indications, pitfalls, and specific interventions. In: Vandereycken W, Kog E, Vanderlinden J, eds. The Family Approach to Eating Disorders: Assessment and Treatment of Anorexia Nervosa and Bulimia. New York, NY: PMA Publishing; 1989:263-310.
8. Woodside DB, Shekter-Wolfson LF, Garfinkel PE, Olmsted MP. Family interactions in bulimia nervosa II: complex intrafamily comparisons and clinical significance. Int J Eat Disord. 1995;17:117-126.
9. Andersen AE. Practical Comprehensive Treatment of Anorexia Nervosa and Bulimia. Baltimore, MD: The Johns Hopkins University Press; 1985:135-148.
10.Pelch BL. Eating disordered families: issues between the generations. In: Lemberg R, Cohn L, eds. Eating Disorders: A Reference Sourcebook. Phoenix, AZ: Oryx Press; 1999:121-123.
11. Moos RH, Moos BS. Family Environment Scale Manual. 2nd ed. Palo Alto, CA: Consulting Psychologists Press; 1986.
12. Waller G, Slade P, Calam R. Family adaptabity and cohesion: relation to eating attitudes and disorders. Int J Eat Disord. 1990;9:225-228.
13. Foley VD. Family therapy. In: Corsini RJ. Current Psychotherapies. 3rd ed. Itasca, IL: FE Peacock Publishers; 1984:447-490.
14. Le Grange D, Eisler I, Dare C, Hodes M. Family criticism and self-starvation: a study of expressed emotion. J Fam Ther. 1992;14:177-192.
15. American Psychiatric Association Work Group on Eating Disorders. Practice guideline for the treatment of patients with eating disorders. Am J Psychiatry. 2000;57(suppl 1):1-39.
16. Brandes J. Outpatient family therapy for bulimia nervosa. In: Woodside DB, Shekter-Wolfson L, eds. Family Approaches in Treatment of Eating Disorders. Washington, DC: American Psychiatric Press; 1991:49-66.
17. Gowers S, Norton K, Halek C, Crisp AH. Outcome of outpatient psychotherapy in a random allocation treatment study of anorexia nervosa. Int J Eat Disord. 1994;15:165-177.
18. Lock J, Le Grange D, Agras WS, Dare C. Treatment Manual for Anorexia Nervosa: A Family-Based Approach. New York, NY: Guilford Press; 2002.
19. Goldner EM, Birminghan CL. Anorexia nervosa: methods of treatment. In: Alexander-Mott L, Lumsden DB, eds. Understanding Eating Disorders: Anorexia Nervosa, Bulimia Nervosa, and Obesity. Washington, DC: Taylor & Francis; 1994:135-157.
20. Michel DM. Psychological assessment as a therapeutic intervention in hospitalized patients with eating disorders. Prof Psychol Res Pract. 2002;33:470-477.
Dare C, Eisler I. Family therapy for anorexia nervosa. In: Garner DM, Garfinkel PE, eds. Handbook of Treatment for Eating Disorders. New York, NY: Guilford Press; 1997.
Le Grange D. Family therapy for adolescent anorexia nervosa. J Clin Psychiatry. 1999;55:727-739.
Lock J, Le Grange D, Agras WS, Dare C. Treatment Manual for Anorexia Nervosa: A Family-Based Approach. New York, NY: Guilford Press; 2002.
Michel DM, Willard SG. Family evaluation and therapy in anorexia nervosa, bulimia nervosa, and binge eating disorder. In: Brewerton TD, ed. Eating Disorders. New York, NY: Marcel Dekker. In Press.
Michel DM, Willard SG. When Dieting Becomes Dangerous: A Guide to Understanding and Treating Anorexia and Bulimia. New Haven, CT: Yale University Press; 2003.
Minuchin S, Rosman BL, Baker L. Psychosomatic Families: Anorexia Nervosa in Context. Cambridge, MA: Harvard University Press; 1978.
Root MPP, Fallon P, Friedrich WN. Bulimia: A Systems Approach to Treatment. New York, NY: W.W. Norton and Co.; 1986.
Schwartz RC, Barrett MJ, Saba G. Family therapy for bulimia. In: Garner DM, Garfinkel PE, eds. Handbook of Treatment for Eating Disorders. New York, NY: Guilford Press; 1985.
Selvini-Palazzoli M, Aronson J. Self-Starvation. New York, NY: Jason Aronson; 1974.
Vandereycken W, Kog E, Vanderlinden MA. The Family Approach to Eating Disorders: Assessment and Treatment of Anorexia Nervosa and Bulimia. New York, NY: PMA Publishing; 1989.
Woodside B, Shekter-Wolfson L, Brandes J, Lackstrom J. Eating Disorders and Marriage. New York, NY: Brunner/Mazel; 1993.
Woodside DB, Shekter-Wolfson L, eds. Family Approaches in Treatment of Eating Disorders. Washington, DC:?American Psychiatric Press; 1991.
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