Short-term Selective Serotonin Reuptake Inhibitor Research Articles

Selective Serotonin Reuptake Inhibitor Use and Hip Fracture Risk Among Patients on Hemodialysis

Use of selective serotonin reuptake inhibitors (SSRIs) has been associated with hip fracture risk in the general population. This study examined this relationship among patients with kidney failure treated by hemodialysis, a unique high-risk subpopulation, within which the impact of SSRIs on hip fracture risk remains unexplored. Case-control study. Eligible cases of hip fracture among maintenance hemodialysis patients between January 1, 2009, and September 30, 2015, were identified using the US Renal Data System. Each case was matched on index date with 10 eligible controls. To be eligible, study participants needed to have more than 1 year of Medicare Parts A and B coverage and more than 3 years of Part D coverage. For a separate examination of new short-term SSRI exposure, we selected cases and controls with more than 18 months of Part D coverage and no prior antidepressant use for 1 year. During the 3-year Part D coverage period, use of SSRIs characterized as any (≥1 prescription filled), low, moderate, and high use (<20%, 20%-<80%, and≥80% of days covered by filled prescriptions, respectively). We selected cases using International Classification of Diseases, Ninth Revision codes 820.xx and 821.xx. In addition to 1 of these codes tied to a hospitalization, we required a corresponding surgical procedural code within 7 days of diagnosis. Conditional logistic regression to estimate unadjusted and multivariable-adjusted ORs and 95% CIs. We identified 4,912 cases and 49,120 controls. SSRI use was associated with increased hip fracture risk (adjusted OR, 1.25; 95% CI, 1.17-1.35). Risk for fracture was estimated for any, low, moderate, and high SSRI use: adjusted conditional ORs were 1.25 (95% CI, 1.17-1.35), 1.20 (95% CI, 1.08-1.32), 1.31 (95% CI, 1.18-1.43), and 1.26 (95% CI, 1.12-1.41), respectively. The association between hip fracture events and SSRI use was also seen in the examination of new short-term use (adjusted OR, 1.43; 95% CI, 1.23-1.67). Biomarkers of mineral bone disorder were not captured and accounted for in this analysis. We demonstrated an association between increased hip fracture risk and both long- and new short-term SSRI use. The stronger association with new short-term use may suggestan acute mechanism potentially related to falls.

Impact of SSRI Therapy on Risk of Conversion From Mild Cognitive Impairment to Alzheimer's Dementia in Individuals With Previous Depression.

Depression is associated with an increased risk of Alzheimer's disease. Research has shown that the selective serotonin reuptake inhibitor (SSRI) citalopram decreases amyloid-β generation and plaque load. The authors evaluated the impact of SSRI treatment on CSF biomarkers and progression from mild cognitive impairment (MCI) to Alzheimer's dementia. Data sets from 755 currently nondepressed participants from the longitudinal Alzheimer's Disease Neuroimaging Initiative were evaluated by Kaplan-Meier analysis and analyses of variance and covariance with ApoE4 status and age as covariates. In MCI patients with a history of depression, long-term SSRI treatment (>4 years) was significantly associated with a delayed progression to Alzheimer's dementia by approximately 3 years, compared with short-term SSRI treatment, treatment with other antidepressants, or no treatment and compared with MCI patients without a history of depression. No differences in CSF biomarker levels were observed between treatment groups. Long-term SSRI treatment may delay progression from MCI to Alzheimer's dementia.

Neuropsychiatric debut as a presentation of Guillain-Barré Syndrome: An atypical clinical case and literature review

IntroductionGuillain Barré Syndrome (GBS) is an acute immune-mediated polyneuropathy most frequently presenting two to four weeks after an acute mild-moderately severe infection as progressive muscular weakness of the lower limbs extending proximally with dysreflexia and autonomic dysfunction. While GBS is typically believed to be isolated to the Peripheral Nervous System, Central Nervous System (CNS) and psychiatric manifestations as a sequela of the disease have been described in different imaging and clinical studies. Many variants of presentation of GBS have been recognized, however a case presenting with primarily psychiatric and autonomic dysfunction preceding muscle weakness has not been cited in the literatures to date. Case presentationWe describe a 24-year-old previously healthy male presenting with behavioral symptoms including depression, anxiety, and amnesia, and autonomic dysfunction which preceded muscle weakness by two weeks. CNS imaging and blood work results were unremarkable. GBS was confirmed upon cerebral spinal fluid analysis remarkable for an important cytoalbuminologic dissociation and markedly elevated protein concentration. The patient responded well to five cycles of inpatient plasmapheresis and short-term selective serotonin reuptake inhibitor treatment with complete recovery of both neurological and behavioral symptoms. ConclusionThough GBS is typically considered a peripheral neuropathy, evidence for CNS involvement exists; GBS should be considered within the differential diagnosis, and neurological features should be monitored, in a patient with new onset unclear psychiatric and CNS symptoms.

The Effects of Pretreatment versus De Novo Treatment with Selective Serotonin Reuptake Inhibitors on Short-term Outcome after Acute Ischemic Stroke

Selective serotonin reuptake inhibitors (SSRIs) administered in patients following acute ischemic stroke have shown to improve clinical recovery independently of changes in depression. Animal studies have demonstrated that sustained SSRI treatment is superior to short-term SSRI in evoking neurogenesis but how this benefit translates into humans remains to be answered. We hypothesized that in acute ischemic stroke patients, SSRI treatment started before the event leads to improved short-term outcomes compared to de novo SSRI treatment poststroke. We performed an exploratory analysis in consecutive acute ischemic stroke patients and compared patients already receiving fluoxetine, citalopram, or escitalopram with those who started treatment de novo. Of 2653 screened patients, 239 were included (age, 69 ± 14 years; 42% men, baseline median National Institutes of Health Stroke Scale score, 7 [IQR, 10]). Of these patients, 51 started treatment with SSRI before stroke and 188 were prescribed newly SSRIs during hospitalization. In the adjusted multivariate logistic regression models, SSRI pretreatment was associated with favorable functional outcome at discharge defined as a modified Rankin Scale score of 2 or less (odds ratio [OR], 4.00; 95% confidence interval [CI], 1.68-9.57; P < .005), improved early clinical recovery (OR, 2.35; 95% CI, 1.15-4.81; P = .02), and a trend toward prediction of superior motor recovery (OR, 1.82; 95% CI, .90-3.68; P < .01). Our data suggest that SSRI pretreatment may improve clinical outcomes in the early stages of acute ischemic stroke supporting the hypothesis that prolonged SSRI treatment started prestroke is superior to poststroke SSRI.

Abstract W P379: Pre-treatment with Selective Serotonin Reuptake Inhibitors is Associated with Improved Short-term Outcome in Acute Ischemic Stroke

Background and Purpose: Treatment with Selective Serotonin Reuptake Inhibitors (SSRIs) following acute ischemic stroke was shown to improve functional and motor recovery independently of depression, possibly mediated by long-term mechanisms such as increased brain plasticity. In animal studies, chronic SSRI treatment is superior over short-term SSRI in evoking neurogenesis but the applicability of this observation to humans remains unelucidated. We hypothesized that pre-treatment with SSRI in acute ischemic stroke patients is associated with improved recovery compared to post-stroke SSRI. Subjects and Methods: We performed an exploratory analysis in consecutive acute ischemic stroke patients who were pre-treated or treated de novo either with fluoxetine, citalopram or escitalopram. Effects of SSRI-pre-treatment on short-term clinical (total NIHSS and NIHSS motor items) and functional (mRS) outcome at discharge compared to post-stroke SSRI were assessed using bivariate and multivariate analyses. Results: Of 2653 patients screened, 239 were included (aged 69±14 years, mean±SD; 42% men, baseline median NIHSS 7 [IQR, 10]). Compared to post-stroke SSRI (n=188), in the SSRI pre-treatment group (n=51) favorable functional outcome at discharge (mRS≤2) was more frequent (41% vs. 20%; p=0.002), duration of hospitalization was shorter (median: 7 versus 11 days; p&lt;0.0001), and there was a non-significant trend toward improved motor recovery (decrease in NIHSS motor items ≥2 points or 0-1 at discharge; 63% vs. 49%; p=0.08). However there was no such difference in total NIHSS recovery (≥4 points or 0-1 at discharge; p=n.s.). Pre-treatment with SSRI was an independent predictor of favorable functional outcome (mRS≤2) at discharge (OR: 4.00; 95%CI: 1.68-9.57; p=0.002) after adjusting for age, pre-stroke mRS, baseline NIHSS and IV-thrombolysis. Conclusions: Our data suggest that pre-treatment with SSRI may be linked to early clinical recovery after acute ischemic stroke and support the hypothesis that pre-stroke SSRI might be superior to post-stroke SSRI.

Serum Prolactin and Macroprolactin Levels among Outpatients with Major Depressive Disorder Following the Administration of Selective Serotonin-Reuptake Inhibitors: A Cross-Sectional Pilot Study

Clinical trials evaluating the rate of short-term selective serotonin-reuptake inhibitor (SSRI)-induced hyperprolactinemia have produced conflicting results. Thus, the aim of this study was to clarify whether SSRI therapy can induce hyperprolactinemia and macroprolactinemia. Fifty-five patients with major depressive disorder (MDD) were enrolled in this study. Serum prolactin and macroprolactin levels were measured at a single time point (i.e., in a cross-sectional design). All patients had received SSRI monotherapy (escitalopram, paroxetine, or sertraline) for a mean of 14.75 months. Their mean prolactin level was 15.26 ng/ml. The prevalence of patients with hyperprolactinemia was 10.9% for 6/55, while that of patients with macroprolactinemia was 3.6% for 2/55. The mean prolactin levels were 51.36 and 10.84 ng/ml among those with hyperprolactinemia and a normal prolactin level, respectively. The prolactin level and prevalence of hyperprolactinemia did not differ significantly within each SSRI group. Correlation analysis revealed that there was no correlation between the dosage of each SSRI and prolactin level. These findings suggest that SSRI therapy can induce hyperprolactinemia in patients with MDD. Clinicians should measure and monitor serum prolactin levels, even when both SSRIs and antipsychotics are administered.

Short-term SSRI treatment normalises amygdala hyperactivity in depressed patients

Antidepressant drugs such as selective serotonin re-uptake inhibitors (SSRIs) remediate negative biases in emotional processing in depressed patients in both behavioural and neural outcome measures. However, it is not clear if these effects occur before, or as a consequence of, changes in clinical state. In the present study, we investigated the effects of short-term SSRI treatment in depressed patients on the neural response to fearful faces prior to clinical improvement in mood. Altogether, 42 unmedicated depressed patients received SSRI treatment (10 mg escitalopram daily) or placebo in a randomised, parallel-group design. The neural response to fearful and happy faces was measured on day 7 of treatment using functional magnetic resonance imaging. A group of healthy controls was imaged in the same way. Amygdala responses to fearful facial expressions were significantly greater in depressed patients compared to healthy controls. However, this response was normalised in patients receiving 7 days treatment with escitalopram. There was no significant difference in clinical depression ratings at 7 days between the escitalopram and placebo-treated patients. Our results suggest that short-term SSRI treatment in depressed patients remediates amygdala hyperactivity in response to negative emotional stimuli prior to clinical improvement in depressed mood. This supports the hypothesis that the clinical effects of antidepressant treatment may be mediated in part through early changes in emotional processing. Further studies will be needed to show if these early effects of antidepressant medication predict eventual clinical outcome.

The Relationship Between Single Nucleotide Polymorphisms in 5-HT2A Signal Transduction-Related Genes and the Response Efficacy to Selective Serotonin Reuptake Inhibitor Treatments in Chinese Patients with Major Depressive Disorder

To explore the possible relationship between six single nucleotide polymorphisms (SNPs) (rs6311 and rs6305 of 5-HT2A, rs5443 of Gβ3, rs2230739 of ACDY9, rs1549870 of PDE1A and rs255163 of CREB1, which are all related with 5-HT2A the signal transduction pathway) and the response efficacy to selective serotonin reuptake inhibitor (SSRI) treatments in major depressive disorder (MDD) Chinese. This study included 194 depressed patients to investigate the influence of 6 polymorphisms in 5-HT2A signal transduction-related genes on the efficacy of SSRIs assessed over 1 year. The efficacies of SSRIs on 194 MDD patients were evaluated in an 8-week open-trial study. Over 1 year, a follow-up study was completed for 174 of them to observe the long-term efficacy of SSRIs. The optimal-scaling regression analysis was used for testing the relationship between the different genotypes of five SNPs and the efficacy in MDD. It showed that the patients with rs5443TT and rs2230739GG have a relatively good efficacy in response to short-term SSRIs. We also found that good efficacy appeared in depressed patients with rs2230739GG in response to long-term SSRIs. It suggested that different genotypes of rs5443 and rs2230739 might influence the signal transduction pathways of second message and affect therapeutic efficacy.

A Rare Case of Combined Syndrome of Inappropriate Antidiuretic Hormone Secretion and Fanconi Syndrome in an Elderly Woman

An 83-year-old Japanese woman was admitted to our hospital with severe hyponatremia (sodium, 108 mEq/L [108 mmol/L]), hypokalemia, hypochloridemia, hypocalcemia, hypophosphatemia, and hypouricemia. Despite low plasma osmolarity (232 mOsm/kg [232 mmol/kg]), urine osmolarity (320 mOsm/kg) was greater than that of plasma, and she had increased urinary sodium excretion (88 mEq/L [88 mmol/L]) and an unsuppressed high plasma level of antidiuretic hormone (ADH; 5.5 pg/mL [5.1 pmol/L]). These findings indicated that she had syndrome of inappropriate ADH secretion (SIADH). In addition, she had a generalized reabsorption defect of the proximal tubules, including decreased tubular reabsorption of phosphate, increased fractional excretion of uric acid, glycosuria despite a normal blood glucose level, and panaminoaciduria. Thus, combined SIADH and Fanconi syndrome was diagnosed. The cause was thought to be the antidepressant paroxetine, which is a selective serotonin reuptake inhibitor (SSRI). Several of the abnormal values resolved within 1 week after discontinuation of this drug. Although the precise mechanism responsible was not elucidated, we report an extremely rare case of combined SIADH and Fanconi syndrome, probably caused by short-term SSRI therapy.

Effect of short-term SSRI treatment on cognitive bias in generalised anxiety disorder

There is considerable evidence showing that individuals with generalised anxiety disorder (GAD) selectively process threat-related information, e.g. they have a bias to interpret ambiguous information in a threat-related manner. Cognitive theories of anxiety, which provide the basis of cognitive-behaviour therapy, propose that such processing biases play an important role in causing and maintaining anxiety. Given that treatment with selective serotonin re-uptake inhibitors (SSRIs) appears to be effective for GAD, we examined whether it is successful in removing cognitive bias. The clinical group included 19 patients with a diagnosis of GAD, and the control group consisted of a non-clinical sample of volunteers, matched for age, gender and years in education. The patients were assessed on measures of interpretative bias (homophone task), anxiety and depression before being prescribed an SSRI (paroxetine or citalopram). After 4 weeks, the cognitive task and mood measures were repeated in the patient group. Prior to treatment, the GAD group showed a significantly greater level of threat-related interpretive bias than controls. Following SSRI treatment, there were significant reductions in both interpretive bias and in anxiety levels in the GAD group. Furthermore, individuals who showed greater clinical improvement (e.g. reflected by reduced anxiety scores) showed a correspondingly greater reduction in their cognitive bias. The results suggest that SSRIs are effective in modifying both subjective anxiety levels and threat-related interpretive bias.