Case Reports
cessitating early delivery. Continued study of the effects of both lithium and pregnancy on the function of the kidney will prove useful in the management of acute mania in a pregnant patient. In considering treatment of a patient who has a pregnancy complicated by both preeclampsia and mania. it would be wise to avoid lithium.
Low-dose, high-potency neuroleptics to control the psychotic symptoms would appear to be most useful. Addition of a low dosage of a benzodiazepine such as lorazepam to help control agitation can be considered. Finally, close cooperation and monitoring by both the Obstetrics and Psychiatry Services are essential.
References I. Sitland-Marken PA. Rickman LA. Wells BG. et al: Pharmacological management of acute mania in pregnancy. J elin PsycllOpharmam/9:78-87. 1989 2. Numberg HG: An overview of somatic lreatment of psychosis during pregnancy and post-panum. Gen Hosp Psychiatry 11:328-338. 1989 3. Burgess HA: When a patienl on lithium is pregnant. Am
J Nursing 79: 1989-1990. 1979 4. Lazarus JH: Effect of lithium on the kidney. in Endocrim' and Metaholic Efji'cts of Lithium. New York. Plenum. 1986 5. Davison JM. Lindheimer MD: Hypenension in pregnancy. in Gynem/ogy and Ohstl'trics. edited by Sciarra JJ. Philadelphia. Lippincoll. 19119
Auoxetine and Organic Mood Syndrome F. BESSETTE, D.O. LINDA G. PETERSON, M.D.
ROBERT
ffective illness ~fter ~Iosed ~ead injury has been well descnbed In the hterature. ' -J Saran I has reported three hypotheses for the relationship between head injury and the development of affective symptoms. First, head injury may disrupt brain catecholamine and cholinergic metabolism directly. Second. it may produce neuroendocrine disturbances related to pituitary involvement. Finally, it may disrupt the arousal effects of the mesencephalic formation. I Based on these hypotheses. it might be expected that organic mood syndrome secondary to closed
A
Received October 19. 1990: revised February 5. 1991: accepled March 15. 1991. From Ihe Depanment of Psychiatry. University of Massachusells Medical Center. Worcester. Address reprint requests to Dr. Pelerson. Dept. of Psychiatry. University of Massachusells Medical Center. 55 Lake Ave. Nonh. Worcester. MA 01605. Copyrighl © 1992 The Academy of Psychosomatic Medicine.
224
head injury would respond to antidepressant treatment because the primary effects of most antidepressants are on the monoaminergic systems noted above. It might also be expected, however. that there would be particular difficulty with the anticholinergic side effects of the tricyclic antidepressants because of the cholinergic disturbance in these patients. F1uoxetine is a bicyclic antidepressant that is a potent inhibitor of the presynaptic reuptake of serotonin. 4 Fluoxetine is indicated for the treatment of major depression with efficacy comparable to the tricyclic antidepressants; the frequency of side effects. however. is low and dose related. The most common side effects of fluoxetine are nausea. anxiety, insomnia, anorexia, diarrhea. nervousness, and headache. There is no report on the usefulness of tluoxetine for treating organic mood syndrome after closed head injury. The following is the report of a case PSYCHOSOMATICS
Case Reports
of organic mood syndrome after closed head injury that was effectively treated with fluoxetine.
Case Report Ms. A., a 41-year-old white woman without previous personal or family psychiatric history, presented on November 4, 1987, complaining of having anxiety and depression since her industrial accident in March 1985. Ms. A. had hit the top of her head very hard against a pipe while at work. She attempted to continue working but felt dizzy and faint and was taken to the local hospital where she received two sutures for a scalp laceration. She felt "hot and passed out" during the suturing. Because of her loss of consciousness in the emergency room, she was hospitalized. After 2 days, she was released. Ms. A. reported that she had "not felt right" since the injury, but her primary care physician could not find abnormalities in her routine laboratory examinations, IT scan, or EEG. She felt sad, depressed, very irritable. and tired all the time. She found that she cried very easily, had headaches, and had difficulty concentrating at work. She had trouble sleeping at night, and noises began to bother her. She had episodes of feeling shaky both inside and outside. She had palpitations and some nausea. Her past medical history was noncontributory except for rheumatic fever at age 16. She had no history of substance abuse. Ms. A. saw a neurologist in February 1986 for episodes of fainting; the entire exam was "very normal," including a sleep-deprived EEG. He prescribed imipramine (25 mg qhs) and alprazolam (0.5 mg bid) and then referred her to a psychiatrist for her anxiety and depression. Ms. A. saw the psychiatrist in March 1986. He diagnosed her as having organic mood disorder because of no past personal history or family history of mood disorder. She was treated with antidepressants, including desipramine (150 mg), nortriptyline (50 mg), phenelzine (60 mg), and trazodone (150 mg). The imipramine, started by the neurologist, was stopped after 2 months due to the observation of a cardiac arrhythmia. The desipramine and nortriptyline caused palpitations and were therefore discontinued without any therapeutic effect being observed. Phenelzine caused hypotension and syncope, such that the patient fell down in a store; the phenelzine was then stopped without VOLUME 33· NUMBER 2· SPRING 1992
therapeutic effect after 3 months. She tolerated trazodone with some mood improvement despite a decreased libido, constipation, dry mouth, blurred vision, and anorgasmia. She had suicidal ideation after an attempt to lower the trazodone dose. She later terminated treatment after a disagreement about financial arrangements and was referred to another provider. At that time, Ms. A. was on trazodone ( 150 mg qd), alprazolam (3.6 mg qd), propranolol for palpitations, and prochlorperazine (Compazine) for nausea. She was started on methylphenidate (8 mg tid) in January 1988 to increase her energy, concentration, and attention. At 10 mg tid of methylphenidate, some improvement was noted, but she was more nauseous and tremulous. She was then started on slowrelease methylphenidate in an attempt to minimize side effects, up to a total dosage of 30 mg tid. Cyproheptadine (8 mg) was added in May 1988 for sexual dysfunction and frequent headaches. The patient overdosed on 6 methylphenidate tablets on May 20, 1988, after an argument with her husband and after having been seen that day by both her psychiatrist and therapist, who was about to leave for vacation. Because of the incomplete response, overdose, and side effects, the usefulness of the agent was questioned. The patient continued to complain of having fatigue most of the day and frequent headaches. In July 1988, it was decided to wean Ms. A. off all medications, as medication seemed to be contributing to her fatigue and other complaints rather than improving them. After weaning her from all medication, her libido, sleep, and appetite improved, but she was more depressed in both mood and affect. She was very irritable, refused to go out, had poor concentration, and had persistent lethargy. A trial of tluoxetine (20 mg qh) was initiated for relief of the continued mood disturbance. She responded in 5 weeks with great improvement in her mood and energy and was no longer irritable. She noted further improvement in her appetite and libido. She did, however, develop insomnia. She described the tluoxetine as a "miracle drug."
Discussion
The complete response of this patient to a selective serotonin reuptake inhibitor, compared with the partial response to trazodone and the side effect difficulties and a lack of response to other antidepressant treatments, raises questions about 225
Case Reports
the specific role of disturbance in serotonergic systems after brain injury. The exact nature of the disturbance of serotonin production or metabolism after head injury is still unclear, although the extent of the injury seems to be important. Diffuse damage may produce an increase in the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA),~ whereas more focal frontotemporal trauma may produce a decrease in 5-HIAA. 6 Although focal injury was never documented with Ms. A., it is possible that fluoxetine was beneficial, as was trazodone partially, whereas the more nonspecific treatments were unsuccessful in alleviating the symptoms developed by Ms. A. after her injury. F1uoxetine's low side effect profile also proved beneficial to this patient, who had experienced many adverse effects on other antidepres-
sant medications. Patients suffering from brain injury have been noted to be more sensitive than others to some psychotropic side effects.? Also, in early stages of recovery, because patients may have agitation requiring treatment, a few have been observed to respond well to specific serotonin agents like buspirone x and to respond less well to traditional agents such as neuroleptics, due to sensitivity to side effects. 9 This finding has not been replicated in larger samples, however. In addition, O'Shanick' has observed that the anticholinergic properties of many tricyclic antidepressants may negatively influence cognition and precipitate delirium in some brain injured patients, thereby limiting the usefulness of this group of medications. Finally, this report highlights the possible role of trazodone in the treatment of organic mood disorder.
References I. Saran AS: Depression after minor closed head injury: role of dexamethasone suppression test and antidepressants. J Clin Psychiatry 46:335-338. 1985 2. Violon A. DeMol J: Psychological sequelae after head traumas in adults. Acta Neurochir (Wien) 85:96-102. 1987 3. O'Shanick GJ: Neuropsychiatric sequelae of minor head injury. Ad\" Psychosom Med 16: 173-193. 1986 4. Sommi RW. Crimson ML. Bowden CL: Fluoxetine: a serotonin-specific. second-generation antidepressant. Pharmacotherapy 7( I ): 1-15. 1987 5. Pona M. Bareggi S. Coli ice M. et al: Homovanillic acid and 5-hydroxyindole-acetic acid in the CSF of patients after a severe head injury. tt. Ventricular CSF concentra-
226
6.
7.
8. 9.
tions in acute brain post-traumatic syndromes. Eur NeuroJ 13:545-554.1975 Van Woerkom T. Teelken A. Minderhoud J: Difference in neurotransmiller metabolism in frontotemporal-lobe contusion and diffuse cerebral contusion. Lancet 1:812813. 1977 Barnes R. Veith R. Okimoto J. et al: Efficacy of antipsychotic medications in behaviorally disturbed dementia patients. Am J Psychiatry 139: 1170-1174. 1982 Levine A: Case repon: buspirone and agitation in head injury. Brain In} 2:165-167.1988 Peterson LG. Bongar B: Navane versus haldol: treatment of acute organic mental syndromes in the general hospital. Gen Hosp Psychiatry II :412-417. 1989
PSYCHOSOMATICS
cessitating early delivery. Continued study of the effects of both lithium and pregnancy on the function of the kidney will prove useful in the management of acute mania in a pregnant patient. In considering treatment of a patient who has a pregnancy complicated by both preeclampsia and mania. it would be wise to avoid lithium.
Low-dose, high-potency neuroleptics to control the psychotic symptoms would appear to be most useful. Addition of a low dosage of a benzodiazepine such as lorazepam to help control agitation can be considered. Finally, close cooperation and monitoring by both the Obstetrics and Psychiatry Services are essential.
References I. Sitland-Marken PA. Rickman LA. Wells BG. et al: Pharmacological management of acute mania in pregnancy. J elin PsycllOpharmam/9:78-87. 1989 2. Numberg HG: An overview of somatic lreatment of psychosis during pregnancy and post-panum. Gen Hosp Psychiatry 11:328-338. 1989 3. Burgess HA: When a patienl on lithium is pregnant. Am
J Nursing 79: 1989-1990. 1979 4. Lazarus JH: Effect of lithium on the kidney. in Endocrim' and Metaholic Efji'cts of Lithium. New York. Plenum. 1986 5. Davison JM. Lindheimer MD: Hypenension in pregnancy. in Gynem/ogy and Ohstl'trics. edited by Sciarra JJ. Philadelphia. Lippincoll. 19119
Auoxetine and Organic Mood Syndrome F. BESSETTE, D.O. LINDA G. PETERSON, M.D.
ROBERT
ffective illness ~fter ~Iosed ~ead injury has been well descnbed In the hterature. ' -J Saran I has reported three hypotheses for the relationship between head injury and the development of affective symptoms. First, head injury may disrupt brain catecholamine and cholinergic metabolism directly. Second. it may produce neuroendocrine disturbances related to pituitary involvement. Finally, it may disrupt the arousal effects of the mesencephalic formation. I Based on these hypotheses. it might be expected that organic mood syndrome secondary to closed
A
Received October 19. 1990: revised February 5. 1991: accepled March 15. 1991. From Ihe Depanment of Psychiatry. University of Massachusells Medical Center. Worcester. Address reprint requests to Dr. Pelerson. Dept. of Psychiatry. University of Massachusells Medical Center. 55 Lake Ave. Nonh. Worcester. MA 01605. Copyrighl © 1992 The Academy of Psychosomatic Medicine.
224
head injury would respond to antidepressant treatment because the primary effects of most antidepressants are on the monoaminergic systems noted above. It might also be expected, however. that there would be particular difficulty with the anticholinergic side effects of the tricyclic antidepressants because of the cholinergic disturbance in these patients. F1uoxetine is a bicyclic antidepressant that is a potent inhibitor of the presynaptic reuptake of serotonin. 4 Fluoxetine is indicated for the treatment of major depression with efficacy comparable to the tricyclic antidepressants; the frequency of side effects. however. is low and dose related. The most common side effects of fluoxetine are nausea. anxiety, insomnia, anorexia, diarrhea. nervousness, and headache. There is no report on the usefulness of tluoxetine for treating organic mood syndrome after closed head injury. The following is the report of a case PSYCHOSOMATICS
Case Reports
of organic mood syndrome after closed head injury that was effectively treated with fluoxetine.
Case Report Ms. A., a 41-year-old white woman without previous personal or family psychiatric history, presented on November 4, 1987, complaining of having anxiety and depression since her industrial accident in March 1985. Ms. A. had hit the top of her head very hard against a pipe while at work. She attempted to continue working but felt dizzy and faint and was taken to the local hospital where she received two sutures for a scalp laceration. She felt "hot and passed out" during the suturing. Because of her loss of consciousness in the emergency room, she was hospitalized. After 2 days, she was released. Ms. A. reported that she had "not felt right" since the injury, but her primary care physician could not find abnormalities in her routine laboratory examinations, IT scan, or EEG. She felt sad, depressed, very irritable. and tired all the time. She found that she cried very easily, had headaches, and had difficulty concentrating at work. She had trouble sleeping at night, and noises began to bother her. She had episodes of feeling shaky both inside and outside. She had palpitations and some nausea. Her past medical history was noncontributory except for rheumatic fever at age 16. She had no history of substance abuse. Ms. A. saw a neurologist in February 1986 for episodes of fainting; the entire exam was "very normal," including a sleep-deprived EEG. He prescribed imipramine (25 mg qhs) and alprazolam (0.5 mg bid) and then referred her to a psychiatrist for her anxiety and depression. Ms. A. saw the psychiatrist in March 1986. He diagnosed her as having organic mood disorder because of no past personal history or family history of mood disorder. She was treated with antidepressants, including desipramine (150 mg), nortriptyline (50 mg), phenelzine (60 mg), and trazodone (150 mg). The imipramine, started by the neurologist, was stopped after 2 months due to the observation of a cardiac arrhythmia. The desipramine and nortriptyline caused palpitations and were therefore discontinued without any therapeutic effect being observed. Phenelzine caused hypotension and syncope, such that the patient fell down in a store; the phenelzine was then stopped without VOLUME 33· NUMBER 2· SPRING 1992
therapeutic effect after 3 months. She tolerated trazodone with some mood improvement despite a decreased libido, constipation, dry mouth, blurred vision, and anorgasmia. She had suicidal ideation after an attempt to lower the trazodone dose. She later terminated treatment after a disagreement about financial arrangements and was referred to another provider. At that time, Ms. A. was on trazodone ( 150 mg qd), alprazolam (3.6 mg qd), propranolol for palpitations, and prochlorperazine (Compazine) for nausea. She was started on methylphenidate (8 mg tid) in January 1988 to increase her energy, concentration, and attention. At 10 mg tid of methylphenidate, some improvement was noted, but she was more nauseous and tremulous. She was then started on slowrelease methylphenidate in an attempt to minimize side effects, up to a total dosage of 30 mg tid. Cyproheptadine (8 mg) was added in May 1988 for sexual dysfunction and frequent headaches. The patient overdosed on 6 methylphenidate tablets on May 20, 1988, after an argument with her husband and after having been seen that day by both her psychiatrist and therapist, who was about to leave for vacation. Because of the incomplete response, overdose, and side effects, the usefulness of the agent was questioned. The patient continued to complain of having fatigue most of the day and frequent headaches. In July 1988, it was decided to wean Ms. A. off all medications, as medication seemed to be contributing to her fatigue and other complaints rather than improving them. After weaning her from all medication, her libido, sleep, and appetite improved, but she was more depressed in both mood and affect. She was very irritable, refused to go out, had poor concentration, and had persistent lethargy. A trial of tluoxetine (20 mg qh) was initiated for relief of the continued mood disturbance. She responded in 5 weeks with great improvement in her mood and energy and was no longer irritable. She noted further improvement in her appetite and libido. She did, however, develop insomnia. She described the tluoxetine as a "miracle drug."
Discussion
The complete response of this patient to a selective serotonin reuptake inhibitor, compared with the partial response to trazodone and the side effect difficulties and a lack of response to other antidepressant treatments, raises questions about 225
Case Reports
the specific role of disturbance in serotonergic systems after brain injury. The exact nature of the disturbance of serotonin production or metabolism after head injury is still unclear, although the extent of the injury seems to be important. Diffuse damage may produce an increase in the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA),~ whereas more focal frontotemporal trauma may produce a decrease in 5-HIAA. 6 Although focal injury was never documented with Ms. A., it is possible that fluoxetine was beneficial, as was trazodone partially, whereas the more nonspecific treatments were unsuccessful in alleviating the symptoms developed by Ms. A. after her injury. F1uoxetine's low side effect profile also proved beneficial to this patient, who had experienced many adverse effects on other antidepres-
sant medications. Patients suffering from brain injury have been noted to be more sensitive than others to some psychotropic side effects.? Also, in early stages of recovery, because patients may have agitation requiring treatment, a few have been observed to respond well to specific serotonin agents like buspirone x and to respond less well to traditional agents such as neuroleptics, due to sensitivity to side effects. 9 This finding has not been replicated in larger samples, however. In addition, O'Shanick' has observed that the anticholinergic properties of many tricyclic antidepressants may negatively influence cognition and precipitate delirium in some brain injured patients, thereby limiting the usefulness of this group of medications. Finally, this report highlights the possible role of trazodone in the treatment of organic mood disorder.
References I. Saran AS: Depression after minor closed head injury: role of dexamethasone suppression test and antidepressants. J Clin Psychiatry 46:335-338. 1985 2. Violon A. DeMol J: Psychological sequelae after head traumas in adults. Acta Neurochir (Wien) 85:96-102. 1987 3. O'Shanick GJ: Neuropsychiatric sequelae of minor head injury. Ad\" Psychosom Med 16: 173-193. 1986 4. Sommi RW. Crimson ML. Bowden CL: Fluoxetine: a serotonin-specific. second-generation antidepressant. Pharmacotherapy 7( I ): 1-15. 1987 5. Pona M. Bareggi S. Coli ice M. et al: Homovanillic acid and 5-hydroxyindole-acetic acid in the CSF of patients after a severe head injury. tt. Ventricular CSF concentra-
226
6.
7.
8. 9.
tions in acute brain post-traumatic syndromes. Eur NeuroJ 13:545-554.1975 Van Woerkom T. Teelken A. Minderhoud J: Difference in neurotransmiller metabolism in frontotemporal-lobe contusion and diffuse cerebral contusion. Lancet 1:812813. 1977 Barnes R. Veith R. Okimoto J. et al: Efficacy of antipsychotic medications in behaviorally disturbed dementia patients. Am J Psychiatry 139: 1170-1174. 1982 Levine A: Case repon: buspirone and agitation in head injury. Brain In} 2:165-167.1988 Peterson LG. Bongar B: Navane versus haldol: treatment of acute organic mental syndromes in the general hospital. Gen Hosp Psychiatry II :412-417. 1989
PSYCHOSOMATICS
