Combination Of Fluoxetine Research Articles

Combined therapy with interpersonal psychotherapy adapted for borderline personality disorder: A two-years follow-up

Few investigations evaluated the long-term effects of psychotherapies in borderline personality disorder (BPD). In a previous study, we compared efficacy of combination of fluoxetine and interpersonal psychotherapy adapted to BPD (IPT-BPD) versus single fluoxetine administered for 32 weeks. This study is aimed to investigate whether the results obtained with the addition of IPT-BPD persist during a follow-up period. Forty-four patients who completed the 32 weeks trial underwent 24 months of follow-up receiving fluoxetine 20-40 mg/day. Clinical Global Impression Severity (CGI-S), Hamilton Rating Scales for Depression and Anxiety (HDRS, HARS), Social and Occupational Functioning Assessment Scale (SOFAS), Satisfaction Profile (SAT-P), and Borderline Personality Disorder Severity Index (BPDSI) were repeated at 6, 12, and 24 months. Statistical analysis was performed with the general linear model. Results showed that most of the differences between combined therapy and single pharmacotherapy at the end of the 32 weeks trial were maintained after 24 months follow-up. The addition of IPT-BPD to medication produced greater effects on BPD symptoms (impulsivity and interpersonal relationships) and quality of life (perception of psychological and social functioning) that endured after termination of psychotherapy. On the contrary, different effects on anxiety symptoms and affective instability were lost after 6 months.

Drug Combinations Modulate Stem Cell Proliferation in the Subventricular Zone of 11‐month‐old Rats: Innate Gender Differences Could Explain Alzheimer's Susceptibility

In this study, we tested the effect of 30 days of various drugs and drug combinations on the stem cell proliferation in the subventricular zone (SVZ) of the lateral brain ventricles of middle aged (10–12 month) normal Sprague Dawley rats, looking for any gender differences. The female rats should be post‐menopausal, and showed very low endogenous stem cell proliferation, significantly different from male rats (P<0.0001). Statins (1 mg/kg) and the combination of Fluoxetine (5 mg/kg), Simvastatin (1 mg/kg) and Ascorbic acid significantly increased stem cell proliferation in the anterior and middle SVZ in female rats, while the three drug combination increased stem cell proliferation in the posterior SVZ. In the male rats, Fluoxetine (5 mg/kg) significantly decreased stem cell proliferation in all regions of the SVZ (anterior, middle, and posterior). Simvastatin (1 mg/kg) significantly decreased stem cell proliferation in the anterior SVZ in male rats, but not in the middle or posterior SVZ. When comparing the stem cell proliferation in different regions across the two genders with a 2‐way ANOVA, we found that fluoxetine and simvastatin significantly decreased male stem cell proliferation compared to females, but the drug combinations of fluoxetine and statin or fluoxetine, statin and ascorbic acid removed these gender differences. The decreased innate stem cell proliferation in females post‐menopause may make them more susceptible to Alzheimer's disease, but we have shown the fluoxetine, simvastatin and ascorbic acid might be used to increase stem cell proliferation, potentially delaying onset of the disease.Support or Funding InformationWSU Women's in Science Giving Circle

Screening for Major Depressive Disorder in Children and Adolescents: A Systematic Review for the U.S. Preventive Services Task Force.

Major depressive disorder (MDD) is common among children and adolescents and is associated with functional impairment and suicide. To update the 2009 U.S. Preventive Services Task Force (USPSTF) systematic review on screening for and treatment of MDD in children and adolescents in primary care settings. Several electronic searches (May 2007 to February 2015) and searches of reference lists of published literature. Trials and recent systematic reviews of treatment, test-retest studies of screening, and trials and large cohort studies for harms. Data were abstracted by 1 investigator and checked by another; 2 investigators independently assessed study quality. Limited evidence from 5 studies showed that such tools as the Beck Depression Inventory and Patient Health Questionnaire for Adolescents had reasonable accuracy for identifying MDD among adolescents in primary care settings. Six trials evaluated treatment. Several individual fair- and good-quality studies of fluoxetine, combined fluoxetine and cognitive behavioral therapy, escitalopram, and collaborative care demonstrated benefits of treatment among adolescents, with no associated harms. The review included only English-language studies, narrow inclusion criteria focused only on MDD, high thresholds for quality, potential publication bias, limited data on harms, and sparse evidence on long-term outcomes of screening and treatment among children younger than 12 years. No evidence was found of a direct link between screening children and adolescents for MDD in primary care or similar settings and depression or other health-related outcomes. Evidence showed that some screening tools are accurate and some treatments are beneficial among adolescents (but not younger children), with no evidence of associated harms. Agency for Healthcare Research and Quality.

Abstract WP79: Appropriate Timing of Fluoxetine and Statin Administration Reduces the Risk of Secondary Hemorrhagic Infarct After Ischemic Stroke

Introduction: Ongoing clinical trials are testing the effect of fluoxetine delivered 2-15 days from the onset of an acute ischemic stroke where a majority of patients are taking statins. We hypothesized that earlier drug delivery would result in smaller infarcts. Methods: Endothelin-1-induced strokes were initiated in 10-12 month old Sprague-Dawley rats, targeting the forelimb motor cortex. Combined medications of 5 mg/kg fluoxetine and 1 mg/kg simvastatin were orally administered either beginning 6-12 hours or 20-26 hours after stroke induction and continued daily for 90 days. Infarct volumes were assessed at post-stroke day 91 using Nissl stained coronal brain sections. An unpaired T-test with Welch’s correction for unequal variances was used for statistical comparison of the infarct volumes. Results: Control animals typically had 5-13 mm3 infarct volumes. Animals that received fluoxetine and simvastatin beginning 20-26 hours after stroke induction showed a strong trend of reduced infarct volume (3 ± 0.3447 mm3 SEM, P=0.0563). Earlier drug delivery (6-12 hours after stroke) resulted in significantly larger infarct volumes (15.4 ± 4.260 mm3 SEM, P=0.0157) when the drug groups were directly compared (Fig.1). Examination of the infarct volumes showed that earlier drug delivery induced secondary hemorrhagic infarcts, while later delivery did not (P=0.0427; Fisher’s exact test). Conclusions: There appears to be substantial danger of developing hemorrhagic infarct if the combination of fluoxetine and statin is given within 6-12 hours of stroke induction (RR= 4.36, 95% CI = 0.64-29.5). For that reason, it is crucial to monitor stroke patients for statins and fluoxetine, and withhold the statin for at least 20 hours after stroke onset. Delivery of both drugs after 20-26 hours of stroke onset resulted in significantly reduced infarcts.

Black hairy tongue with a fixed dose combination of olanzapine and fluoxetine.

Black hairy tongue (BHT) is a benign disease characterized by elongated filiform lingual papillae, with a carpet-like appearance of the dorsum of the tongue. It is has been reported to occur with a prevalence ranging from 0.6% to 11.3%. Although its etiology is not fully understood, BHT may be triggered by smoking, excessive coffee or black tea drinking, poor oral hygiene, trigeminal neuralgia, general debilitation, dry mouth as well as certain drugs. We present here a case of a patient with psychosis, depression, and benign prostatic hyperplasia, who developed BHT following treatment with a fixed dose combination (FDC) of olanzapine and fluoxetine and recovered within 3 months after withdrawal of treatment with FDC.

Combination of resveratrol and fluoxetine in an acute model of depression in mice: Prevention of oxidative DNA fragmentation and monoamines degradation

Resveratrol (RSV) is a natural polyphenol with diverse biological activities, including potent hepato-protective and antidepressant-like effects. Fluoxetine (FLX) is one of the most commonly prescribed antidepressant drugs, however; it has recently been postulated to induce liver damage. The present study aimed to assess the benefits of combining half the conventional doses of RSV and FLX in an acute reserpine model of depression. Depression was induced in mice by a single i.p. reserpine injection. Oral administration of FLX (10 mg/kg), RSV (80 mg/kg) or their combination (FLX; 5 mg/kg and RSV; 40mg/kg) started one hour after reserpine injection and daily for the following two consecutive days. Behavioral tests were performed on the third day. Brain monoamines were assessed. Prevention of neurodegeneration and preservation potential of the DNA integrity were determined according to the brain nitric oxide and 8 -hydroxy-2 –deoxyguanosine contents. Effect on oxidative stress in both brain and liver was evaluated. Results revealed that combining half the dose of FLX with RSV showed antidepressant activity that was comparable to the effect of using FLX alone and in conclusion; we recommend that further investigations should be conducted to assess the applicability of using combinations of RSV and FLX to treat depression.

CBT plus medication reduces depression relapse even after treatment has ended

Researchers evaluated the combination of continued fluoxetine plus cognitive behavioral therapy (CBT) aimed at relapse prevention for major depressive disorder (MDD). They wanted to see if the combined medication and CBT would prevent relapse beyond the treatment phase. They found that it did, significantly. Even though patients were no longer going to therapy, those who had gone earlier in treatment had a significantly lower relapse rate, and for those who did relapse, it took three months longer than it did for those who did not get CBT.

Combination Therapy of Salvianolic Acid and Fluoxetine Improves the Cognitive Function of Rats with Chronic Stress-induced Depression

To establish the beneficial effects of salvianolic acid and fluoxetine on the improvement of cognitive function and amelioration of depression-like symptoms of rats with chronic stress-induced depression. Ninety-nine male Sprague-Dawley rats were randomly divided into 5 groups--a control group with no stress challenge and 4 chronic stress groups. Rats assigned to chronic stress groups were exposed to stress for 3 weeks, and then were given placebo, fluoxetine (20 mg/kg), salvianolic acid (40 mg/kg), or combined fluoxetine and salvianolic acid. Body weight of each rat was recorded throughout the study. Sucrose preference test and water maze experiment were performed after chronic stress challenge and after drug treatment to assess the effect of drug treatments on depressive-like symptoms and cognitive function. The sucrose preference test was also performed before chronic stress exposure for baseline measurement. Exposure of rats to chronic stress for 3 weeks significantly reduced body weight and sucrose preference values compared with the no stress control. The water maze experiment showed that chronic stress impaired the spatial learning of rats as well. Treatment of stress-challenged rats with fluoxetine and fluoxetine combined with salvianolic acid resulted in shorter training latency and longer time spent in the target quadrant during the exploration stage of the water maze experiment compared with placebo treatment. Effect of the combined regimen was found more obvious. Combination therapy of salvianolic acid and fluoxetine could alleviate depression-like symptoms and cognitive deficit induced by chronic stress.

Trajectories of Functioning Into Emerging Adulthood Following Treatment for Adolescent Depression

PurposeIt is well established that empirically supported treatments reduce depressive symptoms for most adolescents; however, it is not yet known whether these interventions lead to sustained improvements in global functioning. The goal of this study is to assess the clinical characteristics and trajectories of long-term psychosocial functioning among emerging adults who have experienced adolescent-onset major depressive disorder. MethodsGlobal functioning was assessed using the Clinical Global Assessment Scale for children (participants ≤18 years), the Global Assessment of Functioning (participants ≥ 19 years) and the Health of the Nation Outcome Scales for Adolescents among 196 adolescents who elected to complete 3.5 years of naturalistic follow-up subsequent to their participation in the Treatment for Adolescents with Depression Study. The Treatment for Adolescents with Depression Study examined the efficacy of cognitive behavior therapy, fluoxetine, and the combination of cognitive behavior therapy and fluoxetine (combination treatment) over the course of 36 weeks. Mixed-effects regression models were used to identify trajectories and clinical predictors of functioning over the naturalistic follow-up. ResultsGlobal functioning and achievement of developmental milestones (college, employment) improved over the course of follow-up for most adolescents. Depressive relapse, initial randomization to the placebo group, and the presence of multiple psychiatric comorbidities conferred risk for relatively poorer functioning. ConclusionsFunctioning generally improves among most adolescents who have received empirically supported treatments. However, the presence of recurrent major depressive disorder and multiple psychiatric comorbidities is associated with poorer functioning trajectories, offering targets for maintenance treatment or secondary prevention.

The antidepressant drugs fluoxetine and duloxetine produce anxiolytic-like effects in a schedule-induced polydipsia paradigm in rats

Similar to the time-course for treating depression, several weeks of administration are required for serotonin (5-HT) reuptake inhibitors to produce anxiolytic effects. Previous studies with the schedule-induced polydipsia paradigm (a putative preclinical anxiety model) have shown that repeated administration of antidepressant drugs is necessary to produce a suppression of polydipsia, which is interpreted as an anxiolytic-like effect. The present study sought to expand past findings by evaluating the selective 5-HT reuptake inhibitor (SSRI) fluoxetine and the 5-HT-norepinephrine reuptake inhibitor duloxetine in the schedule-induced polydipsia paradigm with rats. Dose combinations of the α2 adrenoceptor antagonist yohimbine with fluoxetine were also explored to determine whether α2 adrenoceptor antagonism could enhance the anxiolytic-like effects produced by an SSRI. Fluoxetine and duloxetine significantly reduced water intake over the course of daily administrations. Daily treatment with the combination of fluoxetine and yohimbine produced a significantly greater reduction in water intake than fluoxetine alone. The present results confirmed previous findings that inhibition of 5-HT reuptake reduces water consumption in this paradigm. The results for the α2 antagonist yohimbine (in combination with fluoxetine) also indicate that α2 adrenoceptor antagonism may significantly enhance anxiolytic-like effects of SSRIs.

Ketamine-like effects of a combination of olanzapine and fluoxetine on AMPA and NMDA receptor-mediated transmission in the medial prefrontal cortex of the rat

Preclinical studies indicate that the rapid antidepressant effect of ketamine is dependent on activation of AMPA receptors in the medial prefrontal cortex (mPFC) resulting in a prolonged enhancement of glutamatergic transmission in the mPFC. In similarity, addition of atypical antipsychotic drugs (APDs) to SSRIs has also been found to induce a rapid and potent antidepressant effect. Using intracellular recordings in layer V/VI pyramidal cells of the rat mPFC in vitro, we found that a combination of low, clinically relevant concentrations of the atypical APD olanzapine and the SSRI fluoxetine facilitated NMDA and AMPA-induced currents in pyramidal cells via activation of dopamine D1 receptors. A single ketamine injection (10mg/kg, 24h before the experiment) enhanced AMPA-and apparently to some extent also NMDA-induced currents. Our results propose that the rapid and potent antidepressant effects of both treatments may be related to a common mechanism of action, namely facilitation of glutamatergic, in particular AMPA receptor-mediated transmission, in the mPFC.

Increasing Neurogenesis with Fluoxetine, Simvastatin and Ascorbic Acid Leads to Functional Recovery in Ischemic Stroke

Less than 8.5% of ischemic stroke patients receive clot-busting drugs within the narrow time needed to reduce injury. Thus, there is need for an easily-accessible delayed post-stroke drug treatment to improve functional recovery. Various combinations of fluoxetine, simvastatin, and ascorbic acid were given to healthy rats to assess impact on neurogenesis versus controls. Fluoxetine combined with simvastatin and ascorbic acid produced a 19-fold increase in neurogenesis versus controls in healthy rats; fluoxetine alone produced 10-fold increase. We next tried a couple of drug combinations versus control in endothelin-induced stroked rats. Combined fluoxetine/ simvastatin/ascorbic acid treatment, given to stroked rats 20-26 hours after stroke induction and continued for 31 days, produced strong recovery as measured by Montoya staircase test (mean recovery to 85% of pre-stroke function) and Forelimb Asymmetry test (mean recovery to 90% of pre-stroke function). Fluoxetine and ascorbic acid without simvastatin only produced ~50% of recovery produced by the 3-drug combination. Our results indicate that combined treatment of Fluoxetine, simvastatin and ascorbic acid represents a promising delayed stroke treatment that greatly improves functional recovery in rats and warrants further study in human patient populations. This work formed the basis for a patent submission (US20130065924A1) Composition and method for treatment of neurodegeneration.

Effect of sub-optimal doses of fluoxetine plus estradiol on antidepressant-like behavior and hippocampal neurogenesis in ovariectomized rats

Estrogens and antidepressants synergize to reduce depressive symptoms and stimulate neurogenesis and neuroplastic events. The aim of this study was to explore whether the antidepressant-like effect induced by the combination of low doses of estradiol (E2) and fluoxetine (FLX) involves changes in cell proliferation, early survival, morphology and dendrite complexity of hippocampal new-immature neurons. The antidepressant-like effects of E2 and/or FLX were evaluated by the forced swimming test (FST), cell proliferation was determined with the endogenous marker Ki67, survival of newborn cells was established with bromo-deoxiuridine (BrdU) and immature neurons were ascertained by doublecortin (DCX) labeling while their dendrite complexity was evaluated with Sholl analysis. Ovariectomized Wistar rats were randomly assigned to one of the following groups: Vehicle (saline/14 days+Oil/-8h before FST); E2 (saline/14 days + E2 2.5 or 10 μg/rat; -8 h before FST); FLX (1.25 or 10 mg/kg for 14 days + oil -8h before FST), and FLX plus E2 (FLX 1.25 mg/kg for 14 days + E2 2.5 μg/rat -8 h before FST). The combination of sub-threshold doses of FLX plus E2 produced antidepressant-like actions similar to those induced by FLX or E2 given independently at optimal doses. Only FLX at an optimal dose and the combination of FLX plus E2 increased cell proliferation, the number of DCX-labeled immature neurons and the complexity of their dendritic tree, suggesting that these events may be responsible for their antidepressant-like effect.

Why Personalized Treatment Decisions Are Important

Why Personalized Treatment Decisions Are Important

Psychiatric Symptoms in Temporal Lobe Epilepsy with Left Mesial Hippocampal Sclerosis

A 16-year-old woman was referred to us for depression and persistent suicidal and homicidal ideation. From 2010, the patient visited a neurologist due to recurrent grand mal epilepsy, auditory and visual hallucinations, episodic memory loss, and persistent depression. Upon admission, it was revealed through clinical history taking that she had suffered from chronic bullying from same-sex peers and sexual abuse, twice, from an adult male in the neighborhood when she was 10 years old. A brain magnetic resonance imaging study showed left mesial hippocampal sclerosis. The patient exhibited improvement of her psychiatric symptoms after treatment with a combination of fluoxetine (30 mg) and aripiprazole (10 mg). Children and adolescents with epilepsy experience conflicts in the family, challenges at school, stigma, and psychosocial limitations or deprivations due to their comorbid psychiatric symptoms and hence, psychiatric evaluation and early intervention is important when treating these patients.

Serotonin syndrome with a combination of aripiprazole and fluoxetine: a case report.

Serotonin syndrome (SS) is a potentially life-threatening condition associated with increased serotonergic activity in the central nervous system. SS is characterized by a triad of altered mental status, autonomic dysfunction, and neuromuscular abnormalities [Boyer and Shannon, 2005]. The syndrome is, for some authors, a loose term to define the clinical picture at the moderate to severe end of a spectrum of serotonin toxicity, mild symptoms of which include tremor, hyperreflexia, and occasional myoclonus [Gillman and Whyte, 2004]. In the severe forms of toxicity, generalized myoclonus, sustained ankle clonus, and hyperreflexia may occur along with hyperthermia, which is associated with increased mortality [Gillman, 2013]. SS is classically associated with the high doses of a single selective serotonin reuptake inhibitor (SSRI) use, or with a combination of two or more serotonergic agents [Mason et al. 2000]. Fluoxetine is metabolized in the liver by the isoenzymes of the cytochrome P450 system, including CYP2D6 [Blazquez et al. 2012]. The role of CYP2D6 in the metabolism of fluoxetine may be clinically important, as there is a great genetic variability in the function of this enzyme [Gaedigk, 2013]. Aripiprazole, an atypical antipsychotic, which is a partial agonist at the 5-HT1A receptors, is equally metabolized via both CYP3A4 and CYP2D6 isoenzymes [Molden et al. 2006]. Therefore, coadministration with fluoxetine (a potent inhibitor of CYP450 2D6) may significantly increase the plasma concentrations of aripiprazole. On the other hand, aripiprazole has no known effect on fluoxetine metabolism [Boulton et al. 2010]. Here, we describe a case in which increased plasma concentration of aripiprazole due to a drug interaction with fluoxetine led to SS.

The pharmacodynamic properties of lurasidone and their role in its antidepressant efficacy in bipolar disorder

The treatment of bipolar depression is one of the most challenging issues in contemporary psychiatry. Currently only quetiapine, the olanzapine–fluoxetine combination and recently lurasidone are officially FDA-approved against this condition. The neurobiology of bipolar depression and the possible targets of bipolar antidepressant therapy remain elusive. The current study investigated whether the pharmacodynamic properties of lurasidone fit to a previously developed model which was the first to be derived on the basis of the strict combination of clinical and preclinical data with no input from theory or opinion. The authors performed a complete and systematic review of the literature to identify the pharmacodynamic properties of lurasidone. The original model suggests that a constellation of effects on different receptors are necessary but the serotonin reuptake inhibition does not seem to play a significant role for bipolar depression. On the contrary norepinephrine activity seems to be very important. Probably the early antidepressant effect can be achieved through an agonistic activity at 5HT-1A and antagonism at alpha1 noradrenergic and 5-HT2A receptors, but the presence of a norepinephrine reuptake inhibition is essential in order to sustain it. Overall the properties of lurasidone fit well the model and add to its validity. A point that needs clarification is norepinephrine reuptake inhibition which is not yet studied for lurasidone.

Fluoxetine Potentiation of Omega-3 Fatty Acid Antidepressant Effect: Evaluating Pharmacokinetic and Brain Fatty Acid-Related Aspects in Rodents

We previously reported that combined fluoxetine administration at antidepressant doses renders additive antidepressant effects, whereas non-antidepressant doses potentiate the omega-3 fatty acid antidepressant effect. In the present study, we aimed to evaluate putative pharmacokinetic and brain omega-3 fatty acid-related aspects for fluoxetine potentiation of omega-3 fatty acid antidepressant effect in rats. Coadministration of omega-3 fatty acids with a non-antidepressant dose of fluoxetine (1mg/kg day) failed to affect both brain fluoxetine concentration and norfluoxetine plasma concentration profile. Fluoxetine plasma concentrations remained below the sensitivity limit of the detection method. Either antidepressant (10mg/kg day) or non-antidepressant (1mg/kg day) doses of fluoxetine in combination with omega-3 fatty acids increased hippocampal docosapentaenoic acid (DPA, 22:5 omega-3) levels. Although individual treatments had no effects on DPA concentration, DPA increase was higher when omega-3 were combined with the non-antidepressant dose of fluoxetine. Chronic DPA administration exerted antidepressant-like effects in the forced swimming test while increasing hippocampal docosahexaenoic (22:6 omega-3) and DPA levels. Our results suggest no pharmacokinetic interaction and reveal specific hippocampal DPA changes after fluoxetine and omega-3 combined treatments in our experimental conditions. The DPA role in the synergistic effect of fluoxetine and omega-3 combined treatments will be for sure the focus of future studies.

Table of Contents

AbstractDirect comparisons of pharmacotherapy, psychotherapy find neither superiorStudy of injectable antipsychotics finds little difference between newer, older agentsClozapine and contraceptivesMedication treatments show little effect on veterans' PTSD symptomsVenlafaxine comparable to estrogen for women with hot flashesOlanzapine+fluoxetine combination slows relapse in treatment‐resistant depressionHospital costs decline dramatically with naltrexone implant for alcohol useAntidepressants show diverse effects on weight gain over long termAdherence to antidepressants benefits heart outcomes in older patientsOmega‐3 fatty acids reduce tobacco craving in smokersSafety Warnings

Tactile Hallucinations with Fluoxetine and Methylphenidate

[Author Affiliation]Gurvinder Singh Arora. 1 Department of Child and Adolescent Psychiatry, University of Illinois at Chicago, Chicago, Illinois.Harpreet Kaur Arora. 2 Christian Medical College, Vellore, India.Jaskirat Sidhu. 3 New York, New York.Fedra Najjar. 1 Department of Child and Adolescent Psychiatry, University of Illinois at Chicago, Chicago, Illinois.Address correspondence to: Gurvinder Singh Arora, MD, Department of Child and Adolescent Psychiatry, University of Illinois at Chicago, 1747 West Roosevelt Road, Chicago, IL 60608, E-mail: vinciarora@gmail.comTo The Editor:Fluoxetine, a serotonin reuptake inhibitor (SSRI) is a commonly used antidepressant in children. Among all SSRIs, it has the longest half-life (fluoxetine, 4-6 days; norfluoxetine, its metabolite, 9.3 days). Methylphenidate is one of the most commonly used stimulants in children and has a short half-life (2-3 hours). Methylphenidate has been known to cause tactile, visual, and auditory hallucinations at therapeutic doses (Ross 2006). Tactile hallucinations are a rare phenomenon with fluoxetine. There have been reports of hallucinations with the use of fluoxetine in combination with other medications (Achamallah 1992; Bourgeois et al. 1998; Coleman et al. 2003) and when used in other ailments comorbid with depression (Lauterbach 1993; Omar et al. 1995). There is an isolated case report of tactile hallucinations that started when the patient was on a combination of methylphenidate and fluoxetine (Coskun et al. 2008). We present a second case further contributing to the evidence of this serious side effect of tactile hallucinations in a patient on a combination of methylphenidate and fluoxetine, limiting compliance to treatment.Case ReportX was an 8-year-old African American male weighing 28.6 kg, with no past psychiatric history, who was initially brought in by his mother for the treatment of his oppositional behavior and crying spells. On further evaluation, it was determined that he had been hyperactive, impulsive, and inattentive and met criteria for attention-deficit/hyperactivity disorder (ADHD). In addition, he also reported multiple depressive symptoms, including depressed mood, loss of interest, decreased energy level, and poor concentration. He was started on methylphenidate 5 mg twice daily, given the fact that his brother, who had had similar symptoms, responded very well to methylphenidate. Methylphenidate dose was increased to 10 mg twice daily 1 week later. Because the patient's mother reported increased physical aggression on this higher dose, it was titrated down to 5 mg twice daily. The patient was started on fluoxetine 4 mg daily for depression, after having been on methylphenidate for 2 weeks. This regimen was continued for 3 more weeks, after which the methylphenidate dose was increased to 10 mg twice daily, after ascertaining that the increased physical aggression was not caused by methylphenidate. While on this dose of methylphenidate for another week, the patient reported a sensation that he described as crawling over his skin, while he was watching television. He denied any visual or auditory hallucinations. This sensation lasted a few minutes and resolved on its own. Two days later, the patient woke up early because of a similar sensation over his skin and face, looking for ants over his body. He walked with caution, thinking that there might be ants on the floor. The sensation lasted for ∼1 hour and then went away. Subsequently, the patient had this sensation off and on, approximately once a day, and it scared him. These tactile hallucinations were thought to be secondary to methylphenidate. Methylphenidate was discontinued after ∼7 weeks of treatment. The tactile hallucinations persisted even 1 week after methylphenidate was discontinued. Fluoxetine was discontinued as well, a week after stopping methylphenidate. …