Case Reports
Fluoxetine Management of Chronic Abdominal Pain STUART KEVIN
T.
J.
EISENDRATH, M.D.
KODAMA, M.S., M.P.H.
A
ntidepressants. particularly the tricyclic agents. are often useful in the management of chronic pain. They have been shown to be effective in the management of a variety of conditions such as diabetic neuropathy, fibromyalgia, headache. postherpetic neuralgia. and abdominal pain.1.2 Side effects. however, can limit their utility. Because tluoxetine (Prozac) does not produce tricyclic side effects such as orthostatic hypotension. increased heart rate. cardiac conduction toxicity. and anticholinergic effects/ it may prove to be a useful alternative analgesic. This paper describes the successful use of tluoxetine to manage chronic abdominal pain and discusses the theoretical implications of this intervention.
Case Report A 25-year-old. married, obese, white woman with a 4-year history of chronic abdominal pain came to the University of Califomi a at San Francisco (UCSF) Pain Clinic. In the 4 years preceding her initial visit to UCSF. the patient had five abdominal or pelvic procedures. Four years before her initial visit she had a left oophorectomy for a dermoid cyst. She developed midline lower abdominal pain 2 months after that procedure. Five months after the first surgery she had a right partial oophorectomy for a follicular cyst, following clomiphene stimulation to enhance fertility. Nine months later she had a laparoscopy to reduce ovarian adhesions. Then a hysterectomy and right oophorectomy were performed 3 months later because her abdominal pain persisted, and she had failed to conceive despite 2 years of fertility attempts. She was given hormonal replacement VOLUME 33· NUMBER 2· SPRING 1992
with medroxyprogesterone and estradiol. Six months after the hysterectomy, the patient developed acute right lower quadrant pain that resulted in an appendectomy that included lysis of adhesions. Her appendix showed inflammation without evidence of active infection. After the procedure. her persistent pain gradually increased over the next 2 years. The patient's gynecologist completed a thorough gynecological evaluation and gastrointestinal assessment. including an upper and lower gastrointestinal radiographic series and abdominal ultrasound. These examinations failed to reveal any persistent organic problem except the possibility of adhesions without evidence of obstruction. The patient was referred to the Pain Clinic. where at the time of her initial visit she rated her pain as ranging from 5 to 8. on scale in which 0 was no pain and 10 was the worst pain possible. She localized her abdominal pain to the right lower quadrant and described it as a nonradiating. very deep. throbbing pain, that was sensitive to touch. She stated that although eating did not affect the pain, it was increased by vibration, travel, and emotional stress. such as school examinations. Further. she reported taking 2.5 mg of oxycodone (percocet) one to two times per day as prescribed by her gynecologist. The pain did not interfere significantly with her appetite. weight. or sleep. She noted the pain interfered most in her life by decreasing sexual activity with her husband. as it made it hard for her to relax even though intercourse itself did not aggravate the pain. In addition, the pain also interfered with her
Received November 20.1990; revised March 14. 1991; accepted March 26. 1991. From the School of Medicine. University of California. San Francisco. Address reprint requests to Dr. Eisendrath. Box F.401 Pamassus Ave.• San Francisco. CA 94143-0984. Copyright © 1992 The Academy of Psychosomatic Medicine. 227
Case Reports
ability to concentrate on her graduate school studies. Her past nonpsychiatric medical history included migraine headaches at age 9-11 years. Her past psychiatric history included I year of weekly visits with a psychologist during college for mild depression that did not require antidepressant medication. Her social history revealed that the patient had married a few months before the onset of her abdominal pain and had tried unsuccessfully to become pregnant during the first 2 years of her 4-year marriage. Mental status examination revealed an obese woman who described her mood as generally happy, though she had about one crying spell per month because of the abdominal pain. Her affect appeared euthymic. There were no neurovegetative signs or symptoms of depression, evidence of thought disturbance, or cognitive deficit. Her Beck Depression Inventory score was 5 « 10 = normal). The patient entered the Pain Clinic Behavioral program, which included biofeedback, transcutaneous nerve stimulation, and psychotherapy, to explore psychological factors, such as her marital relationship, infertility, or hysterectomy, that might have been related to her pain. After 8 weeks of this program, she had not improved her pain control. Although the patient did not appear clinically depressed, we decided that she might benefit from antidepressant treatment for pain management. Due to patient concerns about weight gain, fluoxetine was selected at a dosage of 20 mg daily; the authors believed fluoxetine 's serotoninergic activity might provide analgesic effects similar to those of tricyclic antidepressants. Within I week of starting fluoxetine, the patient noted that her pain had subsided to a 0 to 1/10 level. The only adverse effect was some insomnia. The pain, however, increased back to baseline (5 to 8/10) after 3 weeks of fluoxetine. Consequently, the dosage was increased to 40 mg/day. One month later the patient reported that her pain had dropped to 0 to 1/10, and she no longer required regular oxycodone. She then tapered the fluoxetine dose back to 20 mg/day due to nausea. At this lower dose, she was free of adverse effects, including nausea and insomnia. After 5 months of good pain control (0 to 2/10) and absence of side effects, the patient's dose was reduced to 20 mg, three times a week. The patient reported continued good pain management 4 months later and had not required any oxycodone in over 5 months. One year after starting fluoxetine, the patient reported improved sexual and school functioning. 228
Discussion
In the above case, as is common with many cases of chronic abdominal pain,5 it seems likely that the patient's abdominal pain was affected by both organic and psychological factors. The history of five surgical procedures and her gynecologist's report raised the likelihood of multiple adhesions as contributing factors. The persistent pain may also have been related to psychological factors stemming from her marriage, infertility, hysterectomy, or psychosocial background. Nonetheless, short-term psychotherapeutic efforts failed to produce relief, and she was not interested in long-term psychotherapy. The absence of a depressed mood and other cognitive and vegetative signs of depression indicated that the patient was not clinically depressed. Therefore, it seems unlikely that the analgesic activity of the tluoxetine regimen was due to the treatment of depression. Although the mechanism by which antidepressants exert pain control directly is unknown, it has been suggested that it is mediated, in part, by the serotoninergic inhibition of nociceptive pathways.' Serotonin is involved in descending central nervous system pathways that inhibit transmission of nociceptive signals from peripheral nociceptors. 6 Because tluoxetine is a highly selective serotonin reuptake blocker, it could have produced analgesia in our patient by enhancing the serotoninergic neurotransmission in the antinociceptive pathways.7,slndeed, tluoxetine has been shown to produce analgesia in rats9 and to potentiate morphine-induced analgesia in a number of animal studies. s Alternatively, it is possible that tluoxetine produced analgesia by serotoninergic effects on the gut. But the fact that the patient's pain was not affected by eating makes this hypothesis less likely. It is also unlikely that tluoxetine produced analgesia by placebo effect, because the patient had already failed to find satisfactory pain relief from various pain medicine regimens, such as oxycodone, as well as biofeedback and psychotherapy. Furthermore, the ability of tluoxetine to manage other chronic pain conditions, such as low back pain' and diabetic neuropathy,7 suggests that it PSYCHOSOMATICS
Case Reports
has a direct analgesic effect. The unique side-effect profile and promising preliminary analgesic responses to fluoxetine suggest that it may prove to be an important
alternative to tricyclic antidepressants in the management of pain. Carefully controlled, double-blind studies are required to evaluate fluoxetine in this new role.
References I. Krishnan KR, France RD: Antidepressants in chronic pain syndromes. Am Fam Physician 39:233-237, 1989 2. Richelson E: The use of tricyclic antidepressants in chronic gastrointestinal pain. J Clin Psychiatry 43:50-55. 1982 3. Abramowicz M (ed): F1uoxetine (Prozac) revisited. Med· ical utler 32:83-85. 1990 4. Clifford DB: Treatment of pain with antidepressants. Am Fam Physician 31: 181-185,1985 5. Eisendrath 5J, Way L, Ostroff JW, et al: Identification of psychogenic abdominal pain. PsychosomaTics 27:70571 1,1986
6. Robens MH: Involvement of serotonin in nociceptive pathways. Drug Design and Delil'ery 4:77-83, 1989 7. Theesen KA, Marsh WR: Relief of diabetic neuropathy with fluoxetine. DlCP 23:572-574.1989 8. Benfield P, Heel RC, Lewis SP: Fluoxetine: a review of its pharmacodynamic and pharmacokinetic propenies, and therapeutic efficacy in depressive illness. Drugs 32: 481-508,1986 9. Messing RB. Phebus L, Fisher LA, et al: Analgesic effect of fluoxetine hydrochloride (Lilly 110140), a specific inhibitor of serotonin uptake. PsychopharmacologyCom· municaTions 1:511-521,1975
Periictal Mania A Case Report DILIP RAMCHANDANI, M.D. SILVANA RIGGIO, M.D,
P
sychiatric disorders occurring in association with epilepsy have been related in time to seizure activity (periictal/postictal)l-4 or unrelated in time (interictal).l.s Interictal psychiatric disorders may occur in a setting of clear consciousness and can resemble functional psychiatric conditions such as schizophrenia, schizoaffective disorder, or mood disorder, primarily depressive. 6 Periictally, mood changes can occur, but usually have been associated with lowered level of consciousness and diffuse EEG slowing. I Recently, Barczak et al. 1 reported three cases of hypomania in association with complex partial seizures. Two of their patients presented in a manic state to a psychiatric hospital, and the third VOLUME 33· NUMBER 2· SPRING 1992
patient developed mania upon clinical recovery from complex partial seizure activity. We report on a patient who is unique in that he had no past psychiatric history. He was euthymic on initial presentation. He developed a clear-cut manic syndrome in a controlled clinical setting upon withdrawal of anticonvulsant medication and resultant increase in seizure activity. Further, like Received August 20, 1990: revised December 10. 1990: accepted December 19, 1990. From the Depanments ofPsychiatry and Neurology, Medical College of Pennsylvania. Address reprint requests to Dr. Ramchandani, Dept. of Psychiatry, Medical College of Pennsylvania, 3300 Henry Ave., Philadelphia, PA 19129. Copyright © 1992 The Academy of Psychosomatic Medicine.
229
Fluoxetine Management of Chronic Abdominal Pain STUART KEVIN
T.
J.
EISENDRATH, M.D.
KODAMA, M.S., M.P.H.
A
ntidepressants. particularly the tricyclic agents. are often useful in the management of chronic pain. They have been shown to be effective in the management of a variety of conditions such as diabetic neuropathy, fibromyalgia, headache. postherpetic neuralgia. and abdominal pain.1.2 Side effects. however, can limit their utility. Because tluoxetine (Prozac) does not produce tricyclic side effects such as orthostatic hypotension. increased heart rate. cardiac conduction toxicity. and anticholinergic effects/ it may prove to be a useful alternative analgesic. This paper describes the successful use of tluoxetine to manage chronic abdominal pain and discusses the theoretical implications of this intervention.
Case Report A 25-year-old. married, obese, white woman with a 4-year history of chronic abdominal pain came to the University of Califomi a at San Francisco (UCSF) Pain Clinic. In the 4 years preceding her initial visit to UCSF. the patient had five abdominal or pelvic procedures. Four years before her initial visit she had a left oophorectomy for a dermoid cyst. She developed midline lower abdominal pain 2 months after that procedure. Five months after the first surgery she had a right partial oophorectomy for a follicular cyst, following clomiphene stimulation to enhance fertility. Nine months later she had a laparoscopy to reduce ovarian adhesions. Then a hysterectomy and right oophorectomy were performed 3 months later because her abdominal pain persisted, and she had failed to conceive despite 2 years of fertility attempts. She was given hormonal replacement VOLUME 33· NUMBER 2· SPRING 1992
with medroxyprogesterone and estradiol. Six months after the hysterectomy, the patient developed acute right lower quadrant pain that resulted in an appendectomy that included lysis of adhesions. Her appendix showed inflammation without evidence of active infection. After the procedure. her persistent pain gradually increased over the next 2 years. The patient's gynecologist completed a thorough gynecological evaluation and gastrointestinal assessment. including an upper and lower gastrointestinal radiographic series and abdominal ultrasound. These examinations failed to reveal any persistent organic problem except the possibility of adhesions without evidence of obstruction. The patient was referred to the Pain Clinic. where at the time of her initial visit she rated her pain as ranging from 5 to 8. on scale in which 0 was no pain and 10 was the worst pain possible. She localized her abdominal pain to the right lower quadrant and described it as a nonradiating. very deep. throbbing pain, that was sensitive to touch. She stated that although eating did not affect the pain, it was increased by vibration, travel, and emotional stress. such as school examinations. Further. she reported taking 2.5 mg of oxycodone (percocet) one to two times per day as prescribed by her gynecologist. The pain did not interfere significantly with her appetite. weight. or sleep. She noted the pain interfered most in her life by decreasing sexual activity with her husband. as it made it hard for her to relax even though intercourse itself did not aggravate the pain. In addition, the pain also interfered with her
Received November 20.1990; revised March 14. 1991; accepted March 26. 1991. From the School of Medicine. University of California. San Francisco. Address reprint requests to Dr. Eisendrath. Box F.401 Pamassus Ave.• San Francisco. CA 94143-0984. Copyright © 1992 The Academy of Psychosomatic Medicine. 227
Case Reports
ability to concentrate on her graduate school studies. Her past nonpsychiatric medical history included migraine headaches at age 9-11 years. Her past psychiatric history included I year of weekly visits with a psychologist during college for mild depression that did not require antidepressant medication. Her social history revealed that the patient had married a few months before the onset of her abdominal pain and had tried unsuccessfully to become pregnant during the first 2 years of her 4-year marriage. Mental status examination revealed an obese woman who described her mood as generally happy, though she had about one crying spell per month because of the abdominal pain. Her affect appeared euthymic. There were no neurovegetative signs or symptoms of depression, evidence of thought disturbance, or cognitive deficit. Her Beck Depression Inventory score was 5 « 10 = normal). The patient entered the Pain Clinic Behavioral program, which included biofeedback, transcutaneous nerve stimulation, and psychotherapy, to explore psychological factors, such as her marital relationship, infertility, or hysterectomy, that might have been related to her pain. After 8 weeks of this program, she had not improved her pain control. Although the patient did not appear clinically depressed, we decided that she might benefit from antidepressant treatment for pain management. Due to patient concerns about weight gain, fluoxetine was selected at a dosage of 20 mg daily; the authors believed fluoxetine 's serotoninergic activity might provide analgesic effects similar to those of tricyclic antidepressants. Within I week of starting fluoxetine, the patient noted that her pain had subsided to a 0 to 1/10 level. The only adverse effect was some insomnia. The pain, however, increased back to baseline (5 to 8/10) after 3 weeks of fluoxetine. Consequently, the dosage was increased to 40 mg/day. One month later the patient reported that her pain had dropped to 0 to 1/10, and she no longer required regular oxycodone. She then tapered the fluoxetine dose back to 20 mg/day due to nausea. At this lower dose, she was free of adverse effects, including nausea and insomnia. After 5 months of good pain control (0 to 2/10) and absence of side effects, the patient's dose was reduced to 20 mg, three times a week. The patient reported continued good pain management 4 months later and had not required any oxycodone in over 5 months. One year after starting fluoxetine, the patient reported improved sexual and school functioning. 228
Discussion
In the above case, as is common with many cases of chronic abdominal pain,5 it seems likely that the patient's abdominal pain was affected by both organic and psychological factors. The history of five surgical procedures and her gynecologist's report raised the likelihood of multiple adhesions as contributing factors. The persistent pain may also have been related to psychological factors stemming from her marriage, infertility, hysterectomy, or psychosocial background. Nonetheless, short-term psychotherapeutic efforts failed to produce relief, and she was not interested in long-term psychotherapy. The absence of a depressed mood and other cognitive and vegetative signs of depression indicated that the patient was not clinically depressed. Therefore, it seems unlikely that the analgesic activity of the tluoxetine regimen was due to the treatment of depression. Although the mechanism by which antidepressants exert pain control directly is unknown, it has been suggested that it is mediated, in part, by the serotoninergic inhibition of nociceptive pathways.' Serotonin is involved in descending central nervous system pathways that inhibit transmission of nociceptive signals from peripheral nociceptors. 6 Because tluoxetine is a highly selective serotonin reuptake blocker, it could have produced analgesia in our patient by enhancing the serotoninergic neurotransmission in the antinociceptive pathways.7,slndeed, tluoxetine has been shown to produce analgesia in rats9 and to potentiate morphine-induced analgesia in a number of animal studies. s Alternatively, it is possible that tluoxetine produced analgesia by serotoninergic effects on the gut. But the fact that the patient's pain was not affected by eating makes this hypothesis less likely. It is also unlikely that tluoxetine produced analgesia by placebo effect, because the patient had already failed to find satisfactory pain relief from various pain medicine regimens, such as oxycodone, as well as biofeedback and psychotherapy. Furthermore, the ability of tluoxetine to manage other chronic pain conditions, such as low back pain' and diabetic neuropathy,7 suggests that it PSYCHOSOMATICS
Case Reports
has a direct analgesic effect. The unique side-effect profile and promising preliminary analgesic responses to fluoxetine suggest that it may prove to be an important
alternative to tricyclic antidepressants in the management of pain. Carefully controlled, double-blind studies are required to evaluate fluoxetine in this new role.
References I. Krishnan KR, France RD: Antidepressants in chronic pain syndromes. Am Fam Physician 39:233-237, 1989 2. Richelson E: The use of tricyclic antidepressants in chronic gastrointestinal pain. J Clin Psychiatry 43:50-55. 1982 3. Abramowicz M (ed): F1uoxetine (Prozac) revisited. Med· ical utler 32:83-85. 1990 4. Clifford DB: Treatment of pain with antidepressants. Am Fam Physician 31: 181-185,1985 5. Eisendrath 5J, Way L, Ostroff JW, et al: Identification of psychogenic abdominal pain. PsychosomaTics 27:70571 1,1986
6. Robens MH: Involvement of serotonin in nociceptive pathways. Drug Design and Delil'ery 4:77-83, 1989 7. Theesen KA, Marsh WR: Relief of diabetic neuropathy with fluoxetine. DlCP 23:572-574.1989 8. Benfield P, Heel RC, Lewis SP: Fluoxetine: a review of its pharmacodynamic and pharmacokinetic propenies, and therapeutic efficacy in depressive illness. Drugs 32: 481-508,1986 9. Messing RB. Phebus L, Fisher LA, et al: Analgesic effect of fluoxetine hydrochloride (Lilly 110140), a specific inhibitor of serotonin uptake. PsychopharmacologyCom· municaTions 1:511-521,1975
Periictal Mania A Case Report DILIP RAMCHANDANI, M.D. SILVANA RIGGIO, M.D,
P
sychiatric disorders occurring in association with epilepsy have been related in time to seizure activity (periictal/postictal)l-4 or unrelated in time (interictal).l.s Interictal psychiatric disorders may occur in a setting of clear consciousness and can resemble functional psychiatric conditions such as schizophrenia, schizoaffective disorder, or mood disorder, primarily depressive. 6 Periictally, mood changes can occur, but usually have been associated with lowered level of consciousness and diffuse EEG slowing. I Recently, Barczak et al. 1 reported three cases of hypomania in association with complex partial seizures. Two of their patients presented in a manic state to a psychiatric hospital, and the third VOLUME 33· NUMBER 2· SPRING 1992
patient developed mania upon clinical recovery from complex partial seizure activity. We report on a patient who is unique in that he had no past psychiatric history. He was euthymic on initial presentation. He developed a clear-cut manic syndrome in a controlled clinical setting upon withdrawal of anticonvulsant medication and resultant increase in seizure activity. Further, like Received August 20, 1990: revised December 10. 1990: accepted December 19, 1990. From the Depanments ofPsychiatry and Neurology, Medical College of Pennsylvania. Address reprint requests to Dr. Ramchandani, Dept. of Psychiatry, Medical College of Pennsylvania, 3300 Henry Ave., Philadelphia, PA 19129. Copyright © 1992 The Academy of Psychosomatic Medicine.
229
