Oral Citalopram Research Articles

Atomoxetine and citalopram alter brain network organisation in Parkinson’s disease

Recent evidence has shown potential cognitive benefits in Parkinson’s disease from restoring neuro- transmitter deficits including noradrenergic and serotonergic transmission. Here, we study global and regional brain network organization using task-free imaging, which minimizes performance confounds and the bias towards predetermined networks. Thirty-three patients with idiopathic Parkinson’s disease were studied three times in a double-blinded, placebo-controlled crossover design, following placebo, 40mg oral atomoxetine or 30mg oral citalopram. Seventy-six controls were scanned without medication to provide normative data. Relative to controls, patients on placebo had executive impairments, which was reflected in dysfunctional network dynamics in terms of reduced clustering coefficient, hub degree and hub centrality. In patients, atomoxetine improved fluency in proportion to plasma concentration (P=0.006, r2=0.24), and improved response inhibition in proportion to increased hub Eigen centrality (P=0.044, r2=0.14). Citalopram did not improve fluency or inhibitory control, but its influence on network integration and efficiency depended on disease severity: clustering (P=0.01, r2=0.22), modularity (P=0.043, r2=0.14) and path length (P=0.006, r2=0.25) increased in patients with milder forms of Parkinson’s disease, but decreased in patients with more advanced disease (UPDRSIII>30). This study supports the use of task-free imaging of brain networks in translational pharmacology of neurodegenerative disorders. We propose that hub connectivity contributes to cognitive performance in Parkinson’s disease, and that noradrenergic treatment strategies can partially restore the neural systems supporting executive function.robinborchert@gmail.com

Comparison of pramipexole and citalopram in the treatment of depression in Parkinson's disease: A randomized parallel-group trial.

Background:Depression is one of the most common neuropsychiatric symptoms in Parkinson's disease (PD). There is little evidence to guide depression treatment in these patients. The aim of this study was to compare citalopram and pramipexole in reducing depressive symptoms in patients with PD.Materials and Methods:In the present 8-week randomized trial, we compared the efficacy of pramipexole versus citalopram in the treatment of depression in PD patients. For this purpose, 44 PD patients with depression randomly received open-label oral citalopram tablets or pramipexole and their depression, quality of life, and daytime sleepiness scores were evaluated at baseline and after the 8-week trial period.Results:The median age of the patients was 64 years, and about 85% of them were male in both groups. The Beck Depression Inventory score, Parkinson's disease summary index (PDSI), and Epworth Sleepiness Scale were significantly decreased (P < 0.05) in both citalopram and pramipexole groups throughout this period and without significant difference (P > 0.05) between these two groups, except for PDSI score which showed significant improvement in pramipexole group compared with citalopram group (P < 0.0001, r = 0.319). There were neither serious adverse effects nor treatment discontinuation due to the adverse effects.Conclusion:The results indicated that both citalopram and pramipexole were effective in the alleviation of depression and improving the quality of life in PD patients; however, pramipexole was seemed to be slightly more beneficial on quality of life in these patients. Therefore, pramipexole seems to be an effective treatment for depression in addition to its benefits for motor symptoms of PD patients.

Commentary on: A randomised placebo-controlled clinical trial on the efficacy of local lidocaine injections and oral citalopram for the treatment of complex regional pain syndrome

The diagnosis and management of complex regional pain syndrome (CRPS) are controversial and fraught with uncertainty. There is no consensus about optimum management, and it could be that a range of different conditions is being grouped under a common diagnosis, which in any event should always be a diagnosis of exclusion.

A randomised placebo-controlled clinical trial on the efficacy of local lidocaine injections and oral citalopram for the treatment of complex regional pain syndrome

BackgroundComplex regional pain syndrome (CRPS) is a neuropathic pain condition with no universally recognised treatment. The study evaluates the efficacy of a therapeutic protocol consisting of oral citalopram and lidocaine injections in patients affected by CRPS. MethodsBetween January 2010 and December 2014, 150 consecutive patients with CRPS were enrolled in the study and randomly assigned into three groups: group one – lidocaine injection and oral citalopram; group two – lidocaine injection and oral placebo; and group three – injective and oral placebo. The Impairment Sum Score (ISS) was used to assess the severity of CRPS before, as well as at regular intervals after treatment commenced. Statistical significance (p < 0.05) was determined by paired t-tests. ResultsThe combined treatment proved to be more effective (ISS 47.6 to 12.6) than local anaesthetic alone (ISS 47.5 to 21.5) and to placebo (ISS 47.2 to 29.9). ConclusionThis study indicates that CRPS may be managed with well-tolerated association of oral citalopram and lidocaine injections.

A CASE SERIES ON LATE-ONSET CATATONIA MISDIAGNOSED AS DELIRIUM

Introduction Catatonia is a neuropsychiatric syndrome characterized by motor, behavioral and autonomic signs. It is associated with psychiatric disorders, neurologic disorders and general medical conditions. However, the literature on the occurrence of catatonia in older adults is limited, Methods We present three cases of late-onset catatonia in older adults diagnosed with major depressive disorder initially diagnosed as delirium. Case 1 is a 66-year -old male with a past medical history of sclerosing cholangitis, ulcerative colitis, cerebrovascular disease presented with gradually progressive symptoms of one-month duration of mutism, staring, immobility, withdrawal, depression and delusions of infidelity following the surgery of a hepatic nodule. Case 2 is a 68-year-old female with a past history of chronic kidney disease presented with a one-year history of general deterioration of health along with decreased psychomotor activity, talk, social interaction decreased food, auditory hallucinations and persecutory delusions along with staring, posturing, mutism, rigidity, negativism and immobility. Case 3 is a 66-year-old female with a past history of major depressive disorder and gradually declining cognitive functions suggestive of major neurocognitive disorder presented with gradually progressive symptoms of mutism, staring, withdrawal, negativism and depressive symptoms of two months duration. On admission, the Bush Francis Catatonia Rating Scale Scores for the cases were 15/69, 15/69 and 13/69, respectively. All the cases had a past psychiatric history of major depressive disorder. They had been initially admitted to the medicine unit for assessment of delirium which was later ruled out by the consultation-liaison psychiatry team. Results Case 1 was treated with an adequate trial of oral citalopram, lorazepam, olanzapine and later with a trial of oral venlafaxine, aripiprazole and mirtazapine without any improvement in symptoms. The course of treatment was complicated by chronic hyponatremia. His catatonic and depressive symptoms resolved after 13 sessions of electroconvulsive therapy (ECT) along with oral venlafaxine 225mg daily and oral aripiprazole 10mg QHS (total days of inpatient hospitalization=60 days) . Case 2 was treated with oral lorazepam 1?mg twice daily for catatonia along with oral fluoxetine 20?mg daily for depression. The course of treatment was complicated by a urinary tract infection (UTI), which was treated with antibiotics. The dose of oral lorazepam was gradually increased to 1.5mg BID, following which the catatonic symptoms subsequently improved. The patient was discharged after lorazepam was gradually tapered and stopped. However, the patient was readmitted after two days due to a relapse of catatonic symptoms. Oral fluoxetine was continued at the same dose and oral lorazepam 1.5mg BID was restarted. The catatonic symptoms gradually subsided and 10 outpatient sessions of ECT was provided following which the depressive symptoms improved in the same medications (total days of inpatient hospitalization=67 days). Case 2, after relevant investigations, was treated with oral sertraline 100mg daily and oral lorazepam 3?mg three times a day following which her depressive and catatonic symptoms resolved(total days of inpatient hospitalization=7 days). Conclusions Our case series demonstrates catatonia can present in older patients and can be initially misdiagnosed with hypoactive delirium due to the sharing of common characteristics like stupor, agitation and decreased psychomotor activity. Medical disorders followed by mood disorders are implicated in the common causes of catatonia in older adults. The treatment of the cause along with benzodiazepenes remains the mainstay of treatment. ECT has been found to effective in medication refractory cases evidenced in two of the above -mentioned cases with literature demonstrating a delaying in diagnosis leading to a refractory response to ECT. Discontinuation of lorazepam can lead to a relapse of symptoms, as evidenced in case 2. Medical problems in older patients can complicate the treatment course while catatonia can also lead to medical complications like hyponatremia and UTI which have occurred in our cases. Catatonia can lead to increased duration high-risk complications in the elderly like myocardial infarction, pulmonary embolism and thrombosis requiring prompt identification and management, preferably in an interdisciplinary hospital setting. Thus, the prompt diagnosis of catatonia is important and to be differentiated from delirium in older adults as the management differs in both conditions. In this context, consultation-liaison or geriatric psychiatry services becomes essential in a general hospital setting for identification and care of such cases. This research was funded by: Not applicable

Dose-dependent effects of the selective serotonin reuptake inhibitor citalopram: A combined SPECT and phMRI study.

Background:Serotonin transporter blockers, like citalopram, dose-dependently bind to the serotonin transporter. Pharmacological magnetic resonance imaging (phMRI) can be used to non-invasively monitor effects of serotonergic medication. Although previous studies showed that phMRI can measure the effect of a single dose of serotoninergic medication, it is currently unclear whether it can also detect dose-dependent effects.Aims:To investigate the dose-dependent phMRI response to citalopram and compared this with serotonin transporter occupancy, measured with single photon emission computed tomography (SPECT).Methods:Forty-five healthy females were randomized to pre-treatment with placebo, a low (4 mg) or clinically standard (16 mg) oral citalopram dose. Prior to citalopram, and 3 h after, subjects underwent SPECT scanning. Subsequently, a phMRI scan with a citalopram challenge (7.5 mg intravenously) was conducted. Change in cerebral blood flow in response to the citalopram challenge was assessed in the thalamus and occipital cortex (control region).Results:Citalopram dose-dependently affected serotonin transporter occupancy, as measured with SPECT. In addition, citalopram dose-dependently affected the phMRI response to intravenous citalopram in the thalamus (but not occipital cortex), but phMRI was less sensitive in distinguishing between groups than SPECT. Serotonin transporter occupancy showed a trend-significant correlation to thalamic cerebral blood flow change.Conclusion:These results suggest that phMRI likely suffers from higher variation than SPECT, but that these techniques probably also assess different functional aspects of the serotonergic synapse; therefore phMRI could complement positron emission tomography/SPECT for measuring effects of serotonergic medication.

Atomoxetine and citalopram alter brain network organization in Parkinson's disease.

Parkinson’s disease has multiple detrimental effects on motor and cognitive systems in the brain. In contrast to motor deficits, cognitive impairments in Parkinson’s disease are usually not ameliorated, and can even be worsened, by dopaminergic treatments. Recent evidence has shown potential benefits from restoring other neurotransmitter deficits, including noradrenergic and serotonergic transmission. Here, we study global and regional brain network organization using task-free imaging (also known as resting-state), which minimizes performance confounds and the bias towards predetermined networks. Thirty-three patients with idiopathic Parkinson’s disease were studied three times in a double-blinded, placebo-controlled counter-balanced crossover design, following placebo, 40 mg oral atomoxetine (selective noradrenaline reuptake inhibitor) or 30 mg oral citalopram (selective serotonin reuptake inhibitor). Neuropsychological assessments were performed outside the scanner. Seventy-six controls were scanned without medication to provide normative data for comparison to the patient cohort. Graph theoretical analysis of task-free brain connectivity, with a random 500-node parcellation, was used to measure the effect of disease in placebo-treated state (versus unmedicated controls) and pharmacological intervention (drug versus placebo). Relative to controls, patients on placebo had executive impairments (reduced fluency and inhibitory control), which was reflected in dysfunctional network dynamics in terms of reduced clustering coefficient, hub degree and hub centrality. In patients, atomoxetine improved fluency in proportion to plasma concentration (P = 0.006, r2 = 0.24), and improved response inhibition in proportion to increased hub Eigen centrality (P = 0.044, r2 = 0.14). Citalopram did not improve fluency or inhibitory control, but its influence on network integration and efficiency depended on disease severity: clustering (P = 0.01, r2 = 0.22), modularity (P = 0.043, r2 = 0.14) and path length (P = 0.006, r2 = 0.25) increased in patients with milder forms of Parkinson’s disease, but decreased in patients with more advanced disease (Unified Parkinson’s Disease Rating Scale motor subscale part III > 30). This study supports the use of task-free imaging of brain networks in translational pharmacology of neurodegenerative disorders. We propose that hub connectivity contributes to cognitive performance in Parkinson’s disease, and that noradrenergic treatment strategies can partially restore the neural systems supporting executive function.

Serotonin transporter occupancy by the SSRI citalopram predicts default-mode network connectivity

The default mode network (DMN) is an important connectivity hub, and alterations may play a role in the pathophysiology of several neuropsychiatric disorders. Despite the growing body of research on DMN (dys)function, the underlying neurochemical substrate remains to be elucidated. The serotonergic neurotransmitter system has been suggested to play a substantial role in modulating the DMN. Therefore, we investigated the association between serotonin transporter (SERT) occupancy by the selective serotonin reuptake inhibitor citalopram and DMN functional connectivity. Forty-five healthy female volunteers (mean age = 21.6y) participated in a double-dose study. The subjects were randomized to pre-treatment with placebo, a low (4 mg; ‘low group’) or clinically standard (16 mg; ‘high group’) oral citalopram dose (corresponding to 0%, ∼40% and ∼80% SERT occupancy, respectively). They underwent [123I]FP-CIT single-photon emission computed tomography (SPECT) imaging to assess SERT occupancy. In addition, resting-state functional magnetic resonance imaging was used to measure DMN connectivity. With non-parametric permutation testing we assessed the association between SERT occupancy and DMN connectivity. We found that SERT occupancy by citalopram was negatively associated with DMN connectivity with a number of cortical regions, including the anterior cingulate cortex (ACC), paracingulate gyrus, postcentral gyrus, superior parietal gyrus and temporal pole. These findings provide further neurochemical evidence that the serotonin system dose-dependently modulates DMN function.

The efficacy comparison of citalopram, fluoxetine, and placebo on motor recovery after ischemic stroke: a double-blind placebo-controlled randomized controlled trial

Objective: The present study aimed to assess the effectiveness of oral citalopram, compared with fluoxetine and a placebo, in patients with post-stroke motor disabilities. Design: A randomized double-blind placebo-controlled clinical trial was conducted between January 2015 and January 2016. Setting: The neurology department of a university-affiliated urban hospital in Tehran, Iran. Subjects: Ninety adult patients with acute ischemic stroke, hemiplegia, or hemiparesis and a Fugl-Meyer Motor Scale score of below 55 were included. Interventions: Participants were randomly allocated to one of three groups: Group A received 20 mg PO of fluoxetine daily, Group B received 20 mg PO of citalopram daily, and Group C received a placebo PO The duration of the therapy was 90 days. In addition to the medications, all of the participants received physiotherapy. Main measures: Functional status at 90 days, which was measured by the Fugl-Meyer Motor Scale score. Results: The initial mean (SD) Fugl-Meyer Motor Scale scores for the placebo, fluoxetine, and citalopram groups were 18.2 (11.42), 20.08 (14.53), and 17.07 (14.92), respectively. After 90 days, the scores were 27.96 (18.71) for the placebo group, 52.42 (26.24) for the fluoxetine group, and 50.89 (27.17) for the citalopram group. Compared with the placebo group, the mean Fugl-Meyer Motor Scale scores showed significant increases in the fluoxetine and citalopram groups (P = 0.001). Conclusion: There was no significant difference between citalopram and fluoxetine in facilitating post-stroke motor recovery in ischemic stroke patients. However, compared with a placebo, both drugs improved post-stroke motor function.

Efficacy of Citalopram on Acute Ischemic Stroke Outcome: A Randomized Clinical Trial

Background and purpose. Ischemic stroke (IS) is one of the main causes of death and disability in the adult population, and recovery from it is a major health concern worldwide. The aim of the present study was to evaluate the effectiveness of citalopram on 3-mounth outcome of nondepressed acute IS patients. Methods. In a randomized, placebo-controlled clinical trial, 144 patients with acute IS were studied for 3 months. In one group, the patients received oral citalopram 20 mg (once daily), and in the other group, they received placebo. All patients received standard care, including physiotherapy. Patients with depression were excluded throughout the study. The primary outcome of the study was set to a 50% reduction in the 3-month National Institutes of Health Stroke Scale compared with the baseline scores (Clinical Trial Registration URL: http://www.irct.ir; Unique identifier: IRCT201203192150N2). Results. The mean age of patients was 66.4 years. Of 144 eligible patients, 15 patients died (4 in the citalopram and 11 in the placebo group), and 21 patients did not complete the study follow-up period (10 in the citalopram and 11 in the placebo group). The primary outcome of the study was achieved in 57 patients (79%) in the citalopram and 39 patients (54%) in the placebo group (P < .001), with risk ratio and number needed to treat of 2 (CI = 1.2-3) and 4 (CI = 2.5-8.6), respectively. No major adverse events were found in either group. Conclusions. Citalopram is a safe and tolerable medication in patients with acute IS, which could improve the outcome in these patients.

CITALOPRAM PULSE-LOADING FOR TREATMENT-RESITANT OBSESSIVE-COMPULSIVE DISORDER: PRELIMINARY DATA FROM AN OPEN-LABEL TRIAL

Purpose of the study Treatment resistance is a frequent situation in Obsessive Compulsive Disorder (OCD), occurring in 40–60% of patients. However, in the current literature there are only a few evidence-based options for treatment resistant patients. Pulse-loading treatment consists in a rapid titration of the pharmacological agent in the first days of treatment. A few studies suggested that this kind of titration with intravenous clomipramine could result in a greater and faster response than with a standard titration in OCD resistant patients Koran, 2006 , Grassi, 2013 . The aim of this open-label trial was to investigate the effectiveness and tolerability of a citalopram pulse-loading protocol in severe treatment-resistant OCD patients. Methods We enrolled 7 severe treatment-resistant OCD patients. Treatment-resistance was defined as non-response to two Serotonin Re-uptake Inhibitors (SRIs) trials, one antipsychotic augmentation trial and a non-response to 16 sessions of Cognitive-Behavioral Therapy (CBT) (Pallanti et al., 2002) . After a 2-week washout period from previous SRIs medications, patients were treated with intravenous citalopram starting with 40 mg for 3 days and increasing the dose up to 80 mg from the fourth day. The patients continued the treatment with 80 mg of intravenous citalopram for 18 days (a total of 21 days of intravenous treatment), then they switched to oral treatment (80 mg of oral citalopram). The patients treated with an antipsychotic augmentation, continued their antipsychotic treatment without any change during all the treatment protocol. No cognitive or behavioral psychotherapy was allowed during the intravenous or oral citalopram treatment period. We assessed treatment response using the Yale-Brown Obsessive-Compulsive Scale (YBOCS) and the Clinical Global Impression – Improvement scale (CGI-I) at baseline, week 3 and week 12. The pulse-loading protocol incorporated standard criteria for treatment response (>35% improvement in baseline Y-BOCS scores and a CGI-I of 1 or 2), partial response (≥ 25% improvement in baseline Y-BOCS scores), and non-response ( [3] . Tolerability was assessed with a clinical report form. We assessed putative cardiac side effects with an electrocardiography at baseline, after the fourth day of infusion and before switching to oral therapy, monitoring any QTc change. We also monitored sodium levels during all the course of treatment. Results During the pulse-loading treatment no patients showed significant adverse events. No patients showed clinical significant change of the QTc interval and/or of the sodium levels. Four out of seven patients had a partial or full response at the end-point (3 patients had a full response and 1 patient had a partial response) and one of these had remission. Pulse-loading treatment seemed to induce a faster improvement respect to a standard titration, since the responder patients showed a significant improvement already after 3 weeks. Three out of seven patients did not respond. Conclusion Taking into account the very limited sample size, this case series suggests that this treatment approach deserves further controlled studies.

Paradoxical nocturnal agitation associated with mirtazapine therapy

This report describes an 85 year old woman presenting with a mixed delirium with risk factors of hyponatraemia, polypharmacy, and bilateral frontal lobe atrophy with small vessel cerebrovascular disease. Treatment for depression with oral citalopram had been revised to oral mirtazapine, with the aim of reducing the risks of recurrent hyponatraemia noted with the former. She developed an evolving adverse drug reaction (ADR) symptom profile of insomnia, and later severe paradoxical nocturnal agitation. These symptoms were subsequently noted to correlate with both the night-time dosing pattern, and the increased dosing regimen of the mirtazapine. The symptoms settled rapidly following withdrawal of the mirtazapine. The report briefly reviews the relevant literature, and two previously validated causality assessment systems are applied to the index case to support the pharmacovigilance process. This is aimed at promoting objectivity in assessing for the likelihood that the suspected medication (mirtazapine) was the cause for the noted adverse drug reaction.

Citalopram Pulse-loading for Treatment-resitant Obsessive-compulsive Disorder: Preliminary Data From an Open-label Trial

Introduction Pulse-loading treatment consists in a rapid titration of the pharmacological agent in the first days of treatment. A few studies suggested that this kind of titration with intravenous clomipramine could result in a greater and faster response than with a standard titration in obsessive-compulsive disorder (OCD) resistant patients. The aim of this open-label trial was to investigate the effectiveness and tolerability of a citalopram pulse-loading protocol in severe treatment-resistant OCD patients. Methods We enrolled 8 severe treatment-resistant OCD patients. Patients were treated with intravenous citalopram starting with 40 mg for 3 days and increasing the dose up to 80 mg from the fourth day. The patients continued the treatment with 80 mg of intravenous citalopram for 18 days (a total of 21 days of intravenous treatment), then they switched to oral treatment (80 mg of oral citalopram). Results During the pulse-loading treatment no patients showed significant adverse events. No patients showed clinical significant change of the QTc interval and/or of the sodium levels. Five out of eight patients had a partial or full response at the end-point (4 patients had a full response and 1 patient had a partial response) and two of these had remission. Pulse-loading treatment seemed to induce a faster improvement respect to a standard titration, since the responder patients showed a significant improvement already after 3 weeks. Three out of eight patients did not respond. Conclusion Taking into account the very limited sample size, this case series suggests that this treatment approach deserves further controlled studies

Test–retest reliability of task-related pharmacological MRI with a single-dose oral citalopram challenge

Non-invasive assessment of human neurotransmitter function is a highly valuable tool in clinical research. Despite the current interest in task-based pharmacological MRI (phMRI) for the assessment of neural correlates of serotonin (5-HT) function, test-retest reliability of this technique has not yet been established. Using a placebo-controlled crossover design, we aimed to examine the repeatability of task-related phMRI with a single dose of oral citalopram in twelve healthy female subjects. Since we were interested in the drug's effect on neural correlates of 5-HT related cognitive processes, a sensorimotor and an emotional face processing paradigm were used. For both paradigms, we found no significant effects of the oral citalopram challenge on task-positive brain activity with whole-brain analysis. With ROI-based analysis, there was a small effect of the challenge related to emotional processing in the amygdala, but this effect could not be reproduced between sessions. We did however find reproducible effects of the challenge on task-negative BOLD-responses, particularly in the medial frontal cortex and paracingulate gyrus. In conclusion, our data shows that a single oral dose of citalopram does not reliably affect emotional processing and sensorimotor activity, but does influence task-negative processes in the frontal cortex. This latter finding validates previous studies indicating a role for 5-HT in suppression of the task-negative network during goal-directed behavior.

Citalopram-Associated Gambling: A Case Report

Pathological gambling behaviour is a side effect of dopaminergic drugs used in Parkinson's disease, but has seldom been reported with selective serotonin reuptake inhibitors. A 58-years-old woman with somatisation disorder since the age of 20 and recent-onset major depression (at 54 years) received 40 mg/day intravenous citalopram, thereafter switching to the same dose of oral citalopram to treat her comorbid psychiatric disorders after showing poor response to paroxetine for one year. Her anxious and depressive symptoms were moderately reduced after 7 months of oral citalopram, but simultaneously, the patient admitted gambling. We gradually discontinued citalopram and introduced pregabalin and alprazolam; this was followed by a reduction of gambling compulsions, but the somatisation and depressive symptoms did not further improve. Pathological gambling may be mediated by an interplay of 5-HT1A serotonergic and D2 dopaminergic mechanisms. Citalopram affects both these mechanisms in areas that were shown to be involved in gambling behaviour, but while dopaminergic effects of citalopram appear to be consistent with the induction of gambling, its serotonergic mechanisms are rather inconsistent. In our patient, mood destabilisation induced by citalopram may have contributed to the first onset of pathological gambling.

Citalopram Pulse-Loading for Severe Treatment-Resistant OCD: A Case Series of Acute Response, One Year Follow-Up and Tolerability

Background: Treatment resistance is a frequent situation in Obsessive Compulsive Disorder (OCD), occurring in 40-60% of patients. However, in the current literature there are only a few evidence-based options for treatmentresistant patients. Pulse-loading treatment consists in a rapid titration of the pharmacological agent in the first days of treatment. A few studies suggested that this kind of titration with intravenous clomipramine could result in a greater and faster response than with a standard titration in OCD resistant patients. The main aim of this case series was to investigate the effectiveness and tolerability of a citalopram pulse-loading protocol in severe treatment-resistant OCD patients. Methods: We treated 5 severe treatment-resistant OCD patients with intravenous citalopram starting with 40 mg for 3 days and increasing the dose up to 80 mg from the fourth day. The patients continued the treatment with 80 mgof intravenous citalopram for 18 days (a total of 21 days of intravenous treatment), then they switched to oral treatment (80 mg of oral citalopram). We assessed acute and one-year follow-up efficacy and tolerability. Results: During the pulse-loading treatment no patients showed significant adverse events. Two of five patients had a full response and one of these had remission. Furthermore, these two patients did not have any relapse of OC symptoms during the 1-year follow-up. One of five patients had a partial response after 12 weeks and a full response during the 1-year follow-up period after switching from quetiapine to aripiprazole and after a CBT trial. Two of five patients did not respond. No patients showed clinical significant changes of the QTc interval. No patients showed significant changes of the sodium levels. Conclusion: Taking into account the very limited sample size, this case series suggests that this treatment approach deserves further controlled studies.

Feasibility of ASL-based phMRI with a single dose of oral citalopram for repeated assessment of serotonin function

Assessment of cerebral serotonin (5-HT) function with arterial spin labeling (ASL)-based pharmacological magnetic resonance imaging (phMRI) could be a highly useful tool in clinical psychiatric research. The goal of this study was to verify the reliability of ASL-based phMRI after an oral challenge of a selective serotonin reuptake inhibitor (SSRI) in repeated assessment of cerebral 5-HT function. In a placebo-controlled, within-subject crossover study we investigated the effect of a single oral dose of citalopram on brain cerebral blood flow (CBF) using a pulsed ASL sequence (PASL) in twelve female healthy volunteers. The within-session repeatability of the PASL signal was good for all regions tested (wsCV<15%). Both ROI- and voxel-based analyses revealed small but significant effects of a citalopram challenge on CBF values in 5-HT rich brain regions, among which the frontal gyrus and thalamus. These effects could however not be replicated between sessions, most probably due to the small effect size of the oral citalopram challenge on cerebral blood flow. We therefore conclude that the test-retest reliability of PASL phMRI with an oral citalopram challenge is low, limiting the technique's sensitivity to time-dependent changes and consequently its use as a (clinical) research tool.

Manic Episode Associated With Clarithromycin in a Patient With Medically Treated Depression

To the Editor: Antibiotic-induced mania, or antibiomania, is an uncommon cause of manic episodes.1 Clarithromycin is one of the most frequently implicated antibiotics.1 Here, a case of clarithromycin-associated mania in a patient with medically treated depression is presented. Case report. Mr A, a 53-year-old schoolteacher with a history of depression, developed increasing distractibility while driving on the highway in 2011, elevating to the point at which he had to stop driving. The patient believed he was having a stroke and presented himself to the emergency department. On examination, the patient displayed agitation, pressured and tangential speech, flight of ideas, distractibility, grandiosity, and disorganized behavior. He became increasingly agitated and a “code white” was called; as a result, the patient was restrained and given haloperidol and lorazepam intramuscularly, which calmed him down. Medical workup was negative for another cause of mania. Mr A had been taking oral citalopram 20 mg daily for the last 15 years to treat his depression. He was also taking oral clarithromycin 1,000 mg daily, which had been prescribed for sinusitis 5 days prior to presentation. The patient noted elevated mood, increased pleasure in his job, and requiring less sleep 1 day after starting clarithromycin. The patient was admitted, and clarithromycin and citalopram were discontinued. Three days later, Mr A’s condition was stable, and he had few manic symptoms. He was started on olanzapine, 10 mg at bedtime, and lamotrigine, which was titrated to 50 mg twice daily. The patient was discharged 10 days after admission. Nightingale et al2 described the first cases of clarithromycin-induced mania in 1995 in 2 patients with AIDS who were prescribed clarithromycin to treat a Mycobacterium avium complex infection. About a year later, in 1996, Cone et al3 described the first case of clarithromycin-induced mania in a patient without AIDS who was prescribed clarithromycin for a soft-tissue infection. Four other cases of clarithromycin-induced mania have since been described in which clarithromycin was prescribed for sinusitis or H pylori infection.4–7 In all cases, mania resolved with discontinuation of clarithromycin.2–7 In only 1 case did the patient have a history of depression.5 The mechanism for antibiotic-induced mania is currently unknown, although several theories have been proposed, including raised serum concentration of the antibiotic (leading to higher central nervous system penetration), antibiotic interactions with neurotransmitters, and antibiotic interactions with cortisol and prostaglandins.1 Management of antibiotic-induced mania typically involves discontinuation of the antibiotic and possible addition of mood-stabilizing medications.1,7 In this case, manic symptoms began to subside with discontinuation of clarithromycin. It is not clear whether clarithromycin is the direct cause of the manic episode, but it could be a contributing trigger. However, due to the past history of depression, the high degree of mania, and the occurrence during driving, mood-stabilizing medications were prescribed. Clarithromycin-induced mania is not a common occurrence, but consideration of this phenomenon could be useful in the differential diagnosis of an episode of mania.7

Bioavailability Investigation of Two Different Oral Formulations of Citalopram, a So-called ‘Second Generation’ Antidepressant Drug

Citalopram (CAS 59729-33-8) belongs to the so-called 'second generation' antidepressant drugs and is used for the treatment of patients with major depression or other depressive disorders. In the present study, two different oral citalopram formulations (Citalopram-ratiopharm film-coated tablets as test preparation and tablets of a reference preparation distributed in Germany) were investigated in 20 healthy volunteers in order to prove bioequivalence between both preparations. A single 40 mg oral dose was administered according to an open, randomised, two-period cross-over design in the fasted state. Blood samples for determination of citalopram plasma concentrations were collected at pre-defined time points up to 168 h following drug administration. A wash-out period of 21 days separated both treatment periods. Citalopram plasma concentrations were determined by means of a validated HPLC method with fluorescence detection. Maximum plasma concentrations (Cmax), of 34.77 ng/ml (test) and 34.42 ng/ml (reference) were achieved. Areas under the plasma concentration-time curve (AUC0-infinity) of 1,719.69 ng*h/ml (test) and 1,725.71 ng*h/ml (reference) were determined. The results showed nearly identical rate and extent of drug absorption. Also further pharmacokinetic parameters were well comparable with each other. Thus, tmax showed values of 3.29 h (test) and 3.77 h (reference). The plasma elimination half-life (t1/2) was 42.50 h (test) und 44.46 h (reference). Both primary target parameters Cmax and AUC0-infinity were tested parametrically by analysis of variance (ANOVA). Bioequivalence between test and reference preparation was demonstrated since for both parameters AUC and Cmax the 90 % confidence intervals of the T/R-ratios of logarithmically transformed data were in the generally accepted range of 80 %-125 %.

The Relationship Between the Acute Cerebral Metabolic Response to Citalopram and Chronic Citalopram Treatment Outcome

Given the challenges in the clinical management of geriatric depression, research over the past decade has focused on developing early neurobiological markers of antidepressant treatment response. This study tested the hypothesis that lower baseline glucose metabolism and greater acute cerebral metabolic responses to a single, intravenous (IV) dose of the selective serotonin reuptake inhibitor (SSRI) citalopram would be associated with greater improvement of depressive symptoms after 12 weeks of citalopram treatment in geriatric depression. sixteen geriatric depressed patients underwent two scans to measure cerebral glucose metabolism after administration of either a saline placebo or citalopram infusion (40 mg, IV). Then, the patients were treated with the oral citalopram medication for 12 weeks. greater improvement of depressive symptoms was associated with lower baseline metabolism in anterior cingulate, superior, middle, and inferior frontal gyri (bilaterally), inferior parietal lobule (bilaterally), precuneus (right), insula (left), parahippocampal gyrus (right), caudate (bilaterally), and putamen (left) regions. Greater improvement of depressive symptoms was associated with greater reductions in metabolism after acute citalopram administration in similar brain regions, including additional posterior cortical regions. lower baseline cerebral metabolism and greater decreases with acute citalopram administration are associated with better antidepressant response to chronic citalopram treatment. These data are consistent with previous studies of total sleep deprivation and suggest that dynamic, early adaptive changes or normalization of cerebral metabolism may represent early neurobiological markers of chronic SSRI treatment response in geriatric depression.