Posted by ed_uk on November 12, 2005, at 12:04:15
In reply to Re: Dilantin (PHT), posted by Elroy on November 10, 2005, at 15:02:21
Here are some (little) studies which might be of interest....... Phenytoin seems to have aroused some interest among psychiatrists in Israel.
Summary of the trials performed in Israel................
Int J Neuropsychopharmacol. 2005 Oct 5;:1-6
Phenytoin (Dilantin, Epanutin): an anti-bipolar anticonvulsant?
Bersudsky Y.
Ministry of Health Mental Health Center, Faculty of Health Sciences, Ben Gurion University of the Negev, Beersheva, Israel.
Phenytoin, a classical anticonvulsant has been little studied in bipolar disorder. We completed a trial of phenytoin in mania and schizoaffective disorder, manic type. Thirty-nine patients entered a 5-wk double-blind controlled trial of haloperidol (Haldol)+phenytoin vs. haloperidol+placebo; 30 patients completed at least 3 wk; 25 completed 5 wk. Significantly more improvement was observed in those patients receiving phenytoin. Phenytoin has not previously been studied prophylactically in bipolar patients. Bipolar patients were studied who had at least one episode per year in the previous 2 yr despite ongoing prophylaxis. Patients were stable for a mean of 4 months (range 1-13) before entering the study. Phenytoin or placebo was added to their current therapy in a double-blind cross-over design for 6 months in each phase. Thirty observation periods of 6 months each were studied for 23 patients. Three patients had relapse on phenytoin and nine had relapse on placebo. There was a significant prophylactic effect of phenytoin in bipolar disorder [cox's f test for comparing survival in two groups: f (6, 18)=3.44, p =0.02]. This study suggests prophylactic effects of add-on phenytoin in bipolar illness. However, the number of patients was small and confirmation is necessary. Lamotrigine (Lamictal) has recently been reported to have antidepressant effects. In the past, small studies showed antidepressant effects for carbamazepine (Tegretol) and valproate (Depakote). To determine if such effects could be a class property of other voltage-activated sodium channel blockers such as phenytoin, we performed a double-blind controlled trial of phenytoin vs. fluoxetine (Prozac) in unipolar depression. Thirty-three depressed patients entered the study, and 28 completed at least 3 weeks and were included in data analyses. Weekly Hamilton depression scales for 6 wk showed no difference between fluoxetine and phenytoin. Clearly pharmaceutical company funding for clinical trials or advertising for phenytoin is minimal and this must be taken into account in evaluating literature on phenytoin vs. other drugs. The present data suggests that effects on affective disorder may be common to many anticonvulsants.
More info on the depression study.........
J Clin Psychiatry. 2005 May;66(5):586-90.
Controlled double-blind trial of phenytoin vs. fluoxetine (Prozac) in major depressive disorder.
Nemets B, Bersudsky Y, Belmaker RH.
Stanley Research Center & Beersheva Mental Health Center, Ben-Gurion University of the Negev, Beersheva, Israel.
BACKGROUND: Phenytoin was the first non-sedative anticonvulsant introduced and is still the anticonvulsant most widely used worldwide in neurology. Given the efficacy of the anticonvulsant lamotrigine (Lamictal) in the depressed phase of bipolar disorder, a critical theoretical question is whether other anticonvulsants used in treating bipolar disorder might be similarly effective. We therefore undertook a controlled trial of phenytoin versus fluoxetine (Prozac) in major depressive disorder. METHOD: Data were collected from July 2001 to July 2003. Thirty-three subjects entered the study. All patients met DSM-IV criteria for major depressive disorder and scored a minimum of 18 on the 24-item Hamilton Rating Scale for Depression (HAM-D) at baseline. After a 3-day washout of any previous medications, patients were randomly assigned to fluoxetine or phenytoin in identical capsules. Each capsule contained phenytoin 100 mg or fluoxetine 7 mg plus cornstarch. Patients started with 1 tablet daily and increased every other day until they were taking 1 tablet 3 times daily with meals. Blood phenytoin levels were taken after 1 week, 3 weeks, and 6 weeks, and dosage was adjusted to achieve blood levels of 10 to 20 microg/mL, to a maximum dose of 4 capsules per day or a minimum dose of 2 capsules per day. Fluoxetine patients were assigned dummy blood phenytoin levels by the control psychiatrist such that the treating physician would raise the number of capsules to at least 3 per day (20 mg of fluoxetine). RESULTS: Thirty-three patients entered the study, and 28 (N = 14 in each treatment group) completed at least 3 weeks and were included in the data analysis. Patients who dropped out after week 3 (3 patients) were included in the study as last value carried forward. There was no difference between treatment groups in overall rate of response or speed of response. CONCLUSION: The absence of a placebo arm in our study allows for the possibility that neither treatment was more effective than placebo. However, the exclusion of past fluoxetine (Prozac) nonresponders and the minimum HAM-D score at baseline of 18 make this possibility unlikely.
More info on the bipolar prophylaxis study................
Bipolar Disord. 2003 Dec;5(6):464-7.
Prophylactic effect of phenytoin in bipolar disorder: a controlled study.Mishory A, Winokur M, Bersudsky Y.
Barzilai Hospital, Ashkelon Faculty of Health Sciences, Ministry of Health, Mental Health Center, Ben Gurion University of the Negev, Beersheva, Israel.
OBJECTIVE: Phenytoin is an effective anticonvulsant that has not previously been studied prophylactically in bipolar (BP) patients. Thus a study of phenytoin prophylaxis was undertaken and is herein reported. METHOD: Bipolar patients were studied who had at least one episode per year in the previous 2 years despite ongoing prophylaxis. Patients were stable for a mean of 4 months (range 1-13) before entering the study. Phenytoin or placebo was added to their current therapy in a double-blind cross-over design for 6 months in each phase. Thirty observation periods of 6 months each were studied for 23 patients. RESULTS: Three patients had relapse on phenytoin and nine had relapse on placebo. There was a significant prophylactic effect of phenytoin in BP disorder [Cox's F-test for comparing survival in two groups: F(6, 18) = 3.44, p = 0.02]. CONCLUSIONS: This study suggests prophylactic effects of add-on phenytoin in BP illness. However, the number of patients was small and confirmation is necessary.
More info on the mania trial.............
Am J Psychiatry. 2000 Mar;157(3):463-5.
Phenytoin as an antimanic anticonvulsant: a controlled study.Mishory A, Yaroslavsky Y, Bersudsky Y, Belmaker RH.
Stanley Center for Bipolar Research, Ministry of Health Mental Health Center, Ben Gurion University of the Negev, Beersheva, Israel.
OBJECTIVE: Phenytoin, a classical anticonvulsant, shares with antimanic anticonvulsants the property of blockade of voltage-activated sodium channels. The authors therefore planned a trial of phenytoin for mania. METHOD: Patients with either bipolar I disorder, manic type, or schizoaffective disorder, manic type, entered a 5-week, double-blind controlled trial of haloperidol plus phenytoin versus haloperidol plus placebo. Of 39 patients, 30 completed at least 3 weeks and 25 completed 5 weeks. RESULTS: Significantly more improvement was observed in the patients receiving phenytoin. Added improvement with phenytoin in scores on the Brief Psychiatric Rating Scale and Clinical Global Impression was seen in the patients with bipolar mania but not those with schizoaffective mania. CONCLUSIONS: Blockade of voltage-activated sodium channels may be a common therapeutic mechanism of many anticonvulsants given for mania, and phenytoin may be a therapeutic option for some manic patients.
Phenytoin might rarely induce mania!!
Can J Psychiatry. 1989 Nov;34(8):827-8.
Organic mania induced by phenytoin: a case report.
Patten SB, Klein GM, Lussier C, Sawa R.
Department of Psychiatry, University of Calgary, Alberta.
Organic Mood Disorder of the manic type is a syndrome which resembles a manic episode but is due to a specific organic factor. Organic mania may be associated with a variety of physical illnesses such as temporal lobe epilepsy, multiple sclerosis, neoplasms and hyperthyroidism. In addition, organic mania can be associated with drugs including L-dopa, decongestants, sympathomimetics, steroids, baclofen withdrawal, cimetidine, and possibly captopril. This report describes a case of a 74 year old female who presented with a full syndrome of mania soon after being started on phenytoin. Neither the clinical picture, Mini-mental state score, nor EEG findings were suggestive of delirium. The syndrome resolved soon after the phenytoin was discontinued. This case suggests that phenytoin should be added to the list of medications capable of producing Organic Mood Syndrome, manic type.
Ed
poster:ed_uk
thread:317063
URL: http://www.dr-bob.org/babble/20051112/msgs/578013.html