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B. Kaya, M. Güzelipek, M. E. Özcan Severe Due to and Fluoxetine Combination in a Case of OCD*

Burhanettin Kaya M.D.1, Mehmet Güzelipek M.D.2, M. Erkan Özcan M.D.1

ABSTRACT: ÖZET: SEVERE EXTRAPYRAMIDAL SYMPTOMS DUE TO SULPIRIDE SÜLP‹R‹D VE FLUOKSET‹N’‹N B‹RL‹KTE KULLANIMINA BA⁄LI AND FLUOXETINE COMBINATION IN A CASE OF OCD OLARAK fi‹DDETL‹ EKSTRAP‹RAM‹DAL YAN ETK‹ ORTAYA ÇIKAN B‹R OKB OLGUSU Sulpiride is an agent which has an antidepressant effect in low doses. The combination of in lower Düflük dozlarda kullan›lan sülpiridin antidepresan etkinlik gös- dosages with antidepressants in obsessive-compulsive disorder terdi¤i bilinmektedir. Obsesif kompulsif bozuklu¤un (OKB) (OCD) patients has also been reported to be useful. The case tedavisinde düflük dozlarda antidepresan ilaçlarla birlikte kul- reported was a 53 years old female patient with OCD and major lan›labilmektedir. DSM-V’e göre OKB ve major depresyon tan›s› depression according to the DSM-IV diagnostic criteria. OCD konan 53 yafl›nda bayan hasta. 6 y›ld›r süren OKB’u, 6 ayd›r diagnosis was present for six years and she had been süren depresyonu var. Dirençli OKB olarak kabul edilen ve has- depressied for the last six months. She was accepted as having taneye yat›r›lan hastaya 20 mg/gün fluoksetin baflland›. 1 hafta resistant OCD according to the patient’s history. After she was sonra doz 40 mg’a yükseltildi ve 200 mg sülpirid eklendi. hospitalized, the treatment began with fluoksetin 20 mg/day. In Tedavinin 3. gününde fliddetli ekstrapiramidal yan etkiler ortaya the second week fluoksetin dosage was raised to 40 mg/day ç›kt›. Bunun üzerine sülpirid kesildi. Fluoksetin dozu 20 mg’a inil- and 200 mg/day sulpiride was added. On the third day of com- di. Tedaviye 100 mg/gün difenhidremin, 40 mg/gün propra- bination treatment, severe extrapyramidal symptoms emerged nolol ve 10 mg/gün diazepam eklendi. Bir hafta içinde çi¤neme and this prompted us to quit the use of sulpiride. 3 hareketleri d›fl›ndaki ekstra piramidal sistem belirtilerinde belir- mg/day was ordered in order to relieve those side effects. As gin düzelme gözlendi. these precautions were not efficacious, fluoksetin dosage was lowered to 20 mg/day, and then it was quitted. Anahtar sözcükler: obsesif kompulsif bozukluk, ekstrapiramidal Diphenhidramine 100 mg/day, propranolol 40 mg/day and belirtiler, sülpirid, fluoksetin, ilaç etkileflimi diazepam 10 mg/day were ordered. Except chewing move- ments extrapyramidal symptoms lasted for a week. Klinik Psikofarmokoloji Bülteni 2001;11:121-123

Key words: obsessive-compulsive disorders, extrapyramidal symptoms, sulpiride, fluoksetine, drug interaction

Bull Clin Psychopharmacol 2001;11:121-123

INTRODUCTION study of depressive patients, a single low dose of sulpiride was given and the side effects were moder- bsessive-compulsive disorder (OCD) is a chronic ate sedation, constipation and dry mouth (4). In Odisorder which may frequently be seen with another double-blind comparative study of bipolar major depression and which may also be resistant to depression, sulpiride was combined with . pharmacotherapy (1). Fluoxetine has the advantage Depression and recovered very well and there of carrying both antidepressant and antiobsessive were no side effects (5). effects. Antipsychotics may be added, if the patient This case report discusses a case of OCD and is resistant (2). Sulpiride is a well-known comorbid major depression, who had severe antipsychotic with less side effects below 400 extrapyramidal side effects during a combination mg/day (3). There are limited studies about the anti- treatment with fluoxetine and sulpiride. depressant effect of sulpiride but recent data sug- gests that it is effective in depression and is well tol- Case report erated at 400-1200 mg. Whether this effect is anti- depressant or antipsychotic, it is unknown. In a The case was a 53 years old, female. She had

*This article was presented at Regional Congress of Biological Psychiatry, 3-5 July 2000, ‹stanbul, Turkey 1‹nönü University Medical School Departments of Psychiatry, 2‹nönü University Medical School Departments of Neurology Yaz›flma Adresi / Address reprint requests to: Y. Doç. Dr. Burhanettin Kaya, ‹nönü Ü. T›p Fakültesi, Turgut Özal T›p Merkezi, Psikiyatri AD 44069-Malatya-Turkey Tel: +90 (422) 341 0660/5407 Faks: +90 (422) 341 0728 E-mail: [email protected] Kabul tarihi: 17 Nisan 2001 Klinik Psikofarmakoloji Bülteni, Cilt: 11, Say›: 2, 2001 / Bulletin of Clinical Psychopharmacology, Vol: 11, N.: 2, 2001 121 Severe Extrapyramidal Symptoms Due to Sulpiride and Fluoxetine Combination in a Case of OCD contamination obsession and washing compulsion, fluoxetine and increase the dosage quickly. Sulpiride she could not get out of the bathroom for many was added at a dose of 200 mg/day to accelerate the hours. She had fatigue, weakness, depressive moods, response to treatment. We had to quit sulpiride on diminished pleasure, feeling of hopelessness, suicidal the third day of treatment because of the severe thought and weight loss. Her complaints began extrapyramidal side effects. The Fluoxetine dosage 6 years ago. She has been taking a bath too often was lowered to 20 mg/day and then quitted, and she has been spending more than 9 hours in because severe EPS were continuing. the bathroom everyday. She thought that all liquid In this case, the cause of extrapyramidal side accumulations were , and contaminating her. effects was unclear. It may be because of fluoxetine She had been treated with , haloperi- or sulpiride or both of them. There are reports of dol, and diazepam combinations but they were not extrapyramidal side effects of fluoxetine and sulpiri- effective. She had quitted therapy herself. During the de (6,7). SSRI’s are well-known causes for . previous 6 months she could not get out of the Tremors and dystonic reactions due to SSRI’s are also bathroom, she could not find time and energy for reported. Such events may either be caused by the her routines. She had thoughts of death because she combined use of D2 antagonists or asymptomatic was afraid that she could never improve. Her weight parkinson disorder (8) loss was about 15 kgs in 6 months. Nevertheless the combination of antidepressants Her psyhological examination revealed that her with antipsychotics (especially fluoxetin- physical development was well, she was walking combination) may also cause extrapyramidal symp- slowly and appeared ashamed. She had depressive toms (EPS) (7). It is also reported that the combina- and anxious moods. She had contamination obses- tion of SSRI’s with low a dose of D2 antagonists may sion and washing compulsion. She had hopelessness cause a more apparent increase in production and due to her illness and she had suicidal thoughts. She secretion of in prefrontal knew she was ill but she thought that it was not a projection areas (9). psychological problem. Drug interactions are very important and should Her physical examination and laboratory tests be considered during combination treatments. including complete blood counting, biochemical Cytokrom P450 and other cytokrom systems analyzes, electrocardiogram and radiological exami- have an important role in the therapeutics, effective- nations were as usual. ness, interactions, side effects and these mechanisms She was diagnosed as OCD with major depression are not yet clear (10). according to DSM IV diagnostic criteria. She was Fluoxetin and sulpiride combination may poten- accepted as having resistant OCD according to the tialize each other or may cause elevation in blood patientis history. After she was hospitalized, the levels which may increase the risk for EPS. But there treatment was fluoxetine 20 mg/day in the first are no reports to verify this theory. On the contrary week. In the second week fluoxetine the dosage was in an experimental study with rats, fluoxetin was raised to 40 mg/day and 200 mg/day sulpiride was given with a non-competetive NMDA added. In the third day of combination therapy, antagonist, MK-801, and the combination inhibited severe extrapyramidal symptoms emerged and that the leukomotor hyperactivity (11). EPS in fluoxetine prompted us to quit sulpiride. Biperiden 3 mg/day treatment is rare but in sulpiride treatment it is more was ordered. As these were not efficacious, fluoxe- frequent, although sulpiride is associated with less tine dosage was lowered to 20 mg/day, and then EPS than (12). quitted. Diphenhydramine 100 mg/day, propranolol In the case presented, the treatment period was 40 mg/day and diazepam 10 mg/day were ordered. very short and the dosages were low but extrapyra- Except chewing movements, extrapyramidal symp- midal side effects were severe. We could not find toms lasted for a week. any organic or pathological sign to explain the EPS. Fluoxetine is a cytokrom P-450 2D6 and 3A4 DISCUSSION inhibitor (10). The inhibitor effect of sulpiride on cytokrom P-450 enzyme system has not been The case is a chronic and resistant case which was described yet. Severe extrapyramidal side effects in not treated sufficiently. We planned to begin with the case we report may either be related to cytokrom

122 Klinik Psikofarmakoloji Bülteni, Cilt: 11, Say›: 2, 2001 / Bulletin of Clinical Psychopharmacology, Vol: 11, N.: 2, 2001 B. Kaya, M. Güzelipek, M. E. Özcan

P-450 enzyme system or may just be hypersensivity potantialization between them by increasing blood reaction to sulpiride. There are no reports about levels. interaction of fluoxetine and sulpiride. Combinations of SSRI’s, especially of fluoxetine We suggest that extrapyramidal side effects in with antipsychotics, especially with sulpiride may this case are related with both sulpiride and fluoxe- cause severe EPS, and this may complicate the treat- tine effects on cytokrom P-450 enzyme system or ment.

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