Double Blind Controlled Study of Adding Folic Acid to Fluoxetine in the Treatment of OCD.

BACKGROUND: Folate is important for the synthesis of serotonin the neurotransmitter which plays a main role in OCD. We, therefore, explored the efficacy of folic acid as add on treatment to fluoxetine in a double blind study among patients with OCD. SUBJECTS AND METHODS: A double blind, 12-week study comparing the efficacy of folic acid as add on treatment and placebo in patients with OCD was conducted on thirty six (36) patients. Patients were randomly assigned to folic acid (5 mg/day) or placebo group in addition to fluoxetine (40 mg/day). After the baseline assessment, on week 2, 4, 6, 8 and 12 assessments were performed by using YBOCS, HAM-D, HAM-A and CGI-S. Serum folate, erythrocyte folate, serum homocysteine and B12 levels were measured both baseline and the end of study. RESULTS: A mixed model repeated measures ANCOVA on Y-BOCS scores were used to determine the difference between folic acid and placebo groups. No significant differences were found in the ratios of gender or in the mean age, serum folic acid level, erythrocyte folate level, serum homocysteine level and serum B12 level between the treatment groups at the baseline. Consecutively scores collected over six measurements on YBOCS, HAM-D, HAM-A and CGI showed non-significant differences between folic acid and placebo groups. CONCLUSION: None of the biological markers of one carbon metabolism were associated with the change in YBOCS scores. It may be assumed that there is no beneficial effect of folic acid addition to fluoxetine in the treatment of OCD.

Neurotrophic factors and hippocampal activity in PTSD.

Although numerous studies have investigated the neurotrophic factors and hippocampal activity in posttraumatic stress disorder (PTSD) separately each other, it is unclear whether an association between neurotrophic factors and hippocampal activity is present. The aim of this study was to evaluate the functional changes in hippocampus before and after treatment with escitalopram and to associate these changes with peptides related to neuronal growth in patients with chronic PTSD and trauma survivors without PTSD. Fifteen earthquake survivors with chronic PTSD and thirteen drug naïve trauma exposed individuals without PTSD underwent fMRI scans in a block design. Serum levels of Nerve Growth Factor (NGF) and Brain Derived Neurotrophic Factor (BDNF) were measured before and after 12 weeks treatment with escitalopram. Baseline median serum level of NGF was significantly lower in patients with chronic PTSD than trauma survivors; however, 12 weeks of treatment with escitalopram significantly increased it. Higher activation was found both in left and right hippocampus for chronic PTSD group than trauma survivors. Treatment with escitalopram was significantly associated with suppression of the hyperactivation in left hippocampus in patients with chronic PTSD. Bilateral hyperactivation in hippocampus and lowered NGF may associate with neurobiological disarrangements in chronic PTSD. Treatment with escitalopram was significantly associated with both improvement in the severity of PTSD symptoms and biological alterations. Patients diagnosed with PTSD may have further and complicated deteriorations in hippocampal networks and neurotransmitter systems than individuals who had not been diagnosed with PTSD following the same traumatic experience.

Effect of depression on recovery from PTSD.

It has been suggested that the treatment strategy needs to be reviewed and changed if depression occurs in patients with posttraumatic stress disorder (PTSD). We analyzed data extracted from the Marmara Epidemiological Survey (MES) which had examined 683 survivors at 3 years after a devastating earthquake. Fifty three cases (40.5%) out of the 131 cases with PTSD had also been diagnosed with MDD. Comorbid PTSD and MDD group has significantly lower rates of recovery from PTSD in comparison to PTSD without MDD (26.4% vs. 47.4% respectively). Rates of past psychiatric disorder and past traumatic experience were significantly more frequent among the comorbid group. Moreover, comorbidity of PTSD and MDD was clearly associated with greater psychological distress, more severe PTSD, and diminished perceived social support. Past psychiatric disorder, General Health Questionnaire (GHQ-12) and Multidimensional Scale of Perceived Social Scale (MSPSS) total scores succeeded in predicting the comorbidity of PTSD and MDD significantly.

Clinical and pharmacologic risk factors for neuroleptic malignant syndrome and their association with death.

AIM: The aim of the present study was to evaluate demographics, clinical features, psychiatric diagnoses and prognosis of neuroleptic malignant syndrome (NMS) reported in Turkey, and to assess their association with mortality. METHODS: Data on all reported cases of NMS in the Turkish Psychiatric Index between 1985 and 2005 were collected. The type, dosage and administration period of neuroleptics, the clinical and laboratory findings; and prognosis were compared in terms of mortality. RESULTS: Thirty-six patients with a mean age of 33.67 +/- 16.98 years were identified. Fifteen (41.7%) were diagnosed as having schizophrenia or other psychotic disorders and the same number were diagnosed as having affective disorder. Remaining five (13.9%) were diagnosed with other psychiatric disorders and 1 (2.7%) had no psychiatric diagnosis. Twenty-two (61.1%) of the NMS cases were associated with high potency typical neuroleptics. Association between an atypical antipsychotic and NMS has been reported in one case. NMS appeared within 7 days after initiation of the antipsychotic medication in the majority of samples (n = 19, 52.8%). Several combinations of rescue treatments were used in the majority of cases (n = 19, 52.8%), although bromocriptine (n = 22, 61.1%) was the most frequently preferred rescue treatment for NMS. Benzodiazepines were significantly better than the other treatment options in preventing mortality. Five out of the 36 patients (13.9%) with NMS had died. Age was the only significant independent factor that was associated with mortality. CONCLUSIONS: Benzodiazepines may be included in the treatment of NMS. The mortality rate due to NMS in Turkey was lower than the previously reported rates from other developing countries.

Does gabapentin lead to early symptom improvement in obsessive-compulsive disorder?

OBJECTIVE: The aim of this study was to compare efficacy of fluoxetine alone and co-administration of gabapentin and fluoxetine in patients with obsessive compulsive disorder (OCD). METHODS: Forty outpatients with a DSM-IV diagnosis of OCD were randomized to open label treatment, 20 of whom were treated with fluoxetine alone and the remaining 20 with fluoxetine plus gabapentin during 8 weeks. The severity was assessed by Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and Clinical Global Impression (CGI). RESULTS: Final CGI-I and Y-BOCS scores were not significantly different in both groups. However, in repeated measures ANOVA, compared to fluoxetine group, we found significantly a better improvement in the fluoxetine plus gabapentin group at week 2 by means of YBOCS and CGI-I scores. Comparisons on weeks 4, 6 and 8 revealed no statistical differences between the groups. There was no significant difference of adverse effects between two groups. CONCLUSIONS: Adding gabapentin to fluoxetine in the treatment of OCD seems to shorten the time to onset of fluoxetine's anti-obsessive effect without a significant increase in adverse effects. In order to accelerate the clinical response, co-administration of fluoxetine and gabapentin may be a preferable strategy. On the other hand, further controlled studies are needed to support this finding.

Prevalence of psychiatric disorders three years after the 1999 earthquake in Turkey: Marmara Earthquake Survey (MES).

BACKGROUND: The objective of the study is to describe the community prevalence of psychiatric disorder, mainly posttraumatic stress disorder (PTSD) and Major Depressive Disorder (MDD) 3 years after a devastating earthquake. METHODS: Three years after the Marmara Earthquake, 683 individuals from the epicentre were randomly selected to form a representative sample and were assessed with Composite International Diagnostic Interview (CIDI), General Health Questionnaire (GHQ), Traumatic Stress Symptom Checklist (TSSC) and Beck Depression Inventory (BDI). RESULTS: The 36 months prevalence of PTSD and MDD after the Marmara Earthquake were 19.2% and 18.7% respectively. The current prevalence of PTSD and MDD in the affected community was found to be 11.7% and 10.5%, respectively. PTSD and MDD were the most prevalent disorders after the disaster and showed a decrease over time. However, only 38.9% of the PTSD cases identified at any time over the 3 years were in remission at the 3rd-year. The co-occurrence of MDD with PTSD resulted in a decrease in the rate of recovery from PTSD. MDD was also the most prevalent disorder accompanying PTSD. Of all the subjects 37.5% with PTSD still met the MDD criteria at the 3rd year postearthquake. CONCLUSIONS: In comparison with the data from pre-earthquake national mental health profile, the present study showed that the prevalence of MDD, panic disorder, OCD, GAD, social phobia and special phobias were still higher in the affected region 3 years after the earthquake.

Psychological consequences of the 1999 earthquake in Turkey.

We explored the prevalence of posttraumatic stress disorder (PTSD) and its relation to demographic characteristics and other risk factors for developing PTSD in a large sample (N = 910) of earthquake survivors living in tent city. Twenty-five percent of the sample met DSM-IV criteria for PTSD assessed with the Posttraumatic Stress Disorder Self Test (PTSD-S). Peritraumatic factors explained the most variance when the risk factors were grouped as demographics, pretraumatic, peritraumatic, and posttraumatic. The study emphasized that PTSD among the earthquake victims was as prevalent in Turkey as after disasters in other developing countries but higher than usually found after disasters in developed countries, and there was a relation between some factors-mostly peritraumatic-and PTSD.

Faster response in depressive patients treated with fluoxetine alone than in combination with buspirone.

BACKGROUND: The aim of this study was to compare the antidepressant efficacy of standard dose, dose optimization of antidepressant drug and buspirone augmentation strategies. METHODS: 120 outpatients with a DSM-IV diagnosis of unipolar depression were randomised to 12-weeks of open label treatment with fluoxetine 20 (flx20) or 40 mg (flx40) daily or fluoxetine 20 mg plus buspirone 20 mg daily (flx20-plus-buspirone). The severity of depression was assessed by Hamilton Depression Rating Scale (HDRS). Response was defined as a 50% or greater reduction of the baseline HDRS total score. A response, which began at any time of the study and was maintained until the last visit, was defined as a sustained response. RESULTS: The proportion of responders was not significantly different among the treatment groups at the endpoint. Survival analysis showed, however, a significant faster response in the patients treated with flx20 or flx40 alone than flx20-plus-buspirone. The mean times to onset of a sustained response were 33, 24 and 40 days, respectively. LIMITATIONS: The lack of treatment-resistant group is a methodological limitation of this study. CONCLUSIONS: Adding buspirone to fluoxetine in the treatment of major depressive disorder may delay the time to onset of antidepressant efficacy. In order to accelerate and maximise the clinical response in depressive patients, clinician should prefer to optimize the fluoxetine dose instead of in combination with buspirone.

Fluoxetine once every third day in the treatment of major depressive disorder.

OBJECTIVE: Fluoxetine and its active metabolite norfluoxetine have long half-lives. We postulate that, owing to the long elimination half-life and the time to reach steady-state level in plasma is nearly four weeks, patients diagnosed with major depressive disorder might be treated with fluoxetine taken once every third day, after being treated initially during 4 weeks with daily doses of fluoxetine. METHODS: In this open label, 12-weeks, randomized, prospective study, patients diagnosed with DSM-IV major depressive disorder were randomly assigned into 1 of 3 treatment groups. Thirty-four patients took 20 mg and 32 patients took 40 mg of fluoxetine daily throughout the study. Twenty-nine patients had been taking 20 mg of fluoxetine daily for 4 weeks of the study initially, and then were switched to 20 mg fluoxetine once every third day regime. The severity of depression was assessed by Hamilton Depression Rating Scale (HDRS) and Clinical Global Impressions- Severity Scale (CGI-S). Response was defined as a 50% or greater reduction of the baseline HDRS total score. After defining a strict criterion of relapse, time to relapse was estimated using survival analyses (Kaplan-Meier method). RESULTS: The repeated measures analysis of variance (ANOVA) of HDRS found a significant time effect (F = 464.04, df = 1.00, p < 0.001), but no significant group effects (F = 0.84, df = 2.00,p = 0.433) from baseline through week 12. The proportion of responders was not significantly different between the treatment groups at the endpoint. Survival analyses showed, however, a significant delayed mean time to relapse in patients treated with 40 mg of fluoxetine daily compared to either patients treated with 20 mg of fluoxetine daily or 20 mg fluoxetine once every third day. The mean times to relapse were 79.8, 70.8, and 70.5 days, respectively. Fluoxetine was associated with some adverse events in 46.3% of patients. The most frequently occurring adverse event was insomnia. CONCLUSION: It is proposed that either every third day or daily dosing with the same dose of fluoxetine could treat the patients with major depressive disorder during the acute and continuation period of treatment. Nevertheless, higher daily dose of fluoxetine has a reduced relapse rate compared to that of the lower daily dose.