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Psychiatry Research. Neuroimaging Mar 2024Functional neuroimaging studies have demonstrated abnormal activity and functional connectivity (FC) of the amygdala among individuals with major depressive disorder... (Review)
Review
Functional neuroimaging studies have demonstrated abnormal activity and functional connectivity (FC) of the amygdala among individuals with major depressive disorder (MDD), which may be rectified with selective serotonin reuptake inhibitor (SSRI) treatment. This systematic review aimed to identify changes in the amygdala on functional magnetic resonance imaging (fMRI) scans among individuals with MDD who received SSRIs. A search for fMRI studies examining amygdala correlates of SSRI response via fMRI was conducted through OVID (MEDLINE, PsycINFO, and Embase). The end date was April 4th, 2023. In total, 623 records were screened, and 16 studies were included in this review. While the search pertained to SSRIs broadly, the included studies were escitalopram-, citalopram-, fluoxetine-, sertraline-, and paroxetine-specific. Decreases in event-related amygdala activity were found following 6-to-12-week SSRI treatment, particularly in response to negative stimuli. Eight-week courses of SSRI pharmacotherapy were associated with increased event-related amygdala FC (i.e., with the prefrontal [PFC] and anterior cingulate cortices, insula, thalamus, caudate nucleus, and putamen) and decreased resting-state effective connectivity (i.e., amygdala-PFC). Preliminary evidence suggests that SSRIs may alter amygdala activity and FC in MDD. Additional studies are needed to corroborate findings. Future research should employ long-term follow-ups to determine whether effects persist after treatment termination.
Topics: Humans; Selective Serotonin Reuptake Inhibitors; Depressive Disorder, Major; Magnetic Resonance Imaging; Antidepressive Agents; Amygdala
PubMed: 38183847
DOI: 10.1016/j.pscychresns.2023.111777 -
Frontiers in Psychiatry 2023Vasomotor symptoms, or hot flashes, are among the most common complaints for menopausal and postmenopausal women. As an alternative to hormone replacement therapy,...
INTRODUCTION
Vasomotor symptoms, or hot flashes, are among the most common complaints for menopausal and postmenopausal women. As an alternative to hormone replacement therapy, paroxetine mesylate became the only non-hormonal treatment approved by the U.S. Food and Drug Administration (FDA), despite limited evidence for its efficacy. More specifically, there is uncertainty around paroxetine's unique benefit and the magnitude of the placebo response in clinical trials of paroxetine.
METHODS
Relevant databases were searched to identify randomized clinical trials examining the efficacy of paroxetine to treat hot flashes. The primary outcomes of interest were hot flash frequency and hot flash severity scores. Data was extracted from the published results, and risk of bias assessments were conducted.
RESULTS
Six randomized clinical trials that included a total of 1,486 women were coded and analyzed. The results demonstrated that 79% of the mean treatment response for hot flash frequency is accounted for by a placebo response, resulting in a mean true drug effect of 21% at most. Additionally, 68% of the mean treatment response for hot flash severity is accounted for by a placebo response, resulting in a maximum true drug effect of 32%.
DISCUSSION
The results herein call into question the actual efficacy of the only FDA approved, non-hormonal treatment for hot flashes by demonstrating that a placebo response accounts for the majority of treatment responses for reductions in both hot flash frequency and severity. The findings provide evidence to reevaluate the use of paroxetine to treat postmenopausal hot flashes and emphasize the importance of considering effective, alternative treatments for vasomotor symptoms.
PubMed: 37599891
DOI: 10.3389/fpsyt.2023.1204163 -
Journal of Affective Disorders Jun 2024The impacts of antidepressant pharmacotherapies on cardiovascular risk are unclear. We completed a systematic review with meta-analysis to assess the effect of... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
The impacts of antidepressant pharmacotherapies on cardiovascular risk are unclear. We completed a systematic review with meta-analysis to assess the effect of paroxetine on heart rate variability (HRV) in patients with major depressive disorder (MDD).
METHODS
The searches were accomplished via EMBASE, MEDLINE/PubMed (using the National Library of Medicine), Cochrane Library, CINAHL, Scopus, and Web of Science databases. We included non-blind, single, or double-blind randomized control trials in patients older than 18 diagnosed with MDD. Paroxetine needs to be enforced as a chronic therapeutic medication. We included individual studies that investigated resting HRV.
RESULTS
We documented 402 studies, only following screening and eligibility phases; only six were included (five studies in the meta-analysis). No significant change was noticed for the SDNN index: subtotal = 8.23 [CI: -2.17, 18.63], p = 0.12, I2 = 54 % (very low quality of evidence). A significant change was distinguished for the LF index: subtotal = 0.74 [CI: 0.33, 1.15], p = 0.0004, I2 = 0 % (low quality of evidence). A significant alteration was perceived for the HF index: subtotal = 0.33 [CI: 0.06, 0.6], p = 0.02, I2 = 0 % (low quality of evidence).
CONCLUSION
Meta-analysis demonstrated that paroxetine could advance HRV in MDD patients. Nevertheless, our supposition is founded only on statistical analysis and the very low quality of evidence breakdown reinforces the necessity for further studies to confirm or reject this theory.
Topics: Humans; Paroxetine; Depressive Disorder, Major; Heart Rate; Double-Blind Method; Randomized Controlled Trials as Topic
PubMed: 38513773
DOI: 10.1016/j.jad.2024.03.071 -
Therapeutic Drug Monitoring Apr 2024Compared with antipsychotics, the relationship between antidepressant blood (plasma or serum) concentrations and target engagement is less well-established.
BACKGROUND
Compared with antipsychotics, the relationship between antidepressant blood (plasma or serum) concentrations and target engagement is less well-established.
METHODS
We have discussed the literature on the relationship between plasma concentrations of antidepressant drugs and their target occupancy. Antidepressants reviewed in this work are citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, venlafaxine, duloxetine, milnacipran, tricyclic antidepressants (amitriptyline, nortriptyline, and clomipramine), bupropion, tranylcypromine, moclobemide, and vortioxetine. Four electronic databases were systematically searched.
RESULTS
We included 32 articles published 1996-2022. A strong relationship between serotonin transporter (SERT) occupancy and drug concentration is well established for selective serotonin reuptake inhibitors. Lower limits of recommended therapeutic reference ranges largely corroborate with the findings from positron emission tomography studies (80% SERT occupancy). Only a few novel studies have investigated alternative targets, that is, norepinephrine transporters (NETs), dopamine transporters (DATs), or monoamine oxidase A (MAO-A). For certain classes of drugs, positron emission tomography study data are inconclusive. Low DAT occupancy after bupropion treatment speculates its discussed mechanism of action. For MAO inhibitors, a correlation between drug concentration and MAO-A occupancy could not be established.
CONCLUSIONS
Neuroimaging studies are critical in TDM-guided therapy for certain antidepressants, whereas for bupropion and MAO inhibitors, the available evidence offers no further insight. Evidence for selective serotonin reuptake inhibitors is strong and justifies a titration toward suggested ranges. For SNRIs, duloxetine, and venlafaxine, NETs are sufficiently occupied, well above the SERT efficacy threshold. For these drugs, a titration toward higher concentrations (within the recommended range) should be considered in case of no response at lower concentrations.
Topics: Humans; Selective Serotonin Reuptake Inhibitors; Venlafaxine Hydrochloride; Bupropion; Duloxetine Hydrochloride; Monoamine Oxidase Inhibitors; Antidepressive Agents; Positron-Emission Tomography; Monoamine Oxidase
PubMed: 38287888
DOI: 10.1097/FTD.0000000000001142 -
International Clinical... Jun 2024Currently, there are few pharmacotherapy options for clinicians treating post-traumatic stress disorder (PTSD), and antidepressants are usually the medication of choice....
Currently, there are few pharmacotherapy options for clinicians treating post-traumatic stress disorder (PTSD), and antidepressants are usually the medication of choice. This meta-analysis aimed to review the efficacy of antidepressants in the acute treatment of PTSD in adults while investigating the contribution of study design and placebo response to the findings of these studies. Randomized, double-blind, placebo-controlled clinical trials that compared antidepressants with placebo for acute treatment of PTSD were selected. Standardized mean difference (SMD) in change in Clinician-Administered PTSD Scale scores were pooled after examining for heterogeneity. A random-effects meta-analysis was performed. Twenty-nine antidepressant-placebo comparisons, involving 4575 subjects, were analyzed. The SMD among all studies was 0.25, a small to medium effect size, lower than that in studies of antidepressants in adult major depressive disorder. The SMDs for low and high mean placebo responses, were 0.27 and 0.22, respectively. The overall SMD for paroxetine studies was in the moderate range (0.43) and that for sertraline studies was in the small range (0.12). Our findings suggest that antidepressants have modest efficacy in alleviating PTSD symptoms. Patient-level meta-analyses are required to further explore the potential clinical relevance of sertraline for PTSD.
PubMed: 38869978
DOI: 10.1097/YIC.0000000000000554