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East Asian Archives of Psychiatry :... Jun 2023Clozapine is a potent antipsychotic medication with a complex receptor profile. It is reserved for treatment-resistant schizophrenia. We systematically reviewed studies...
OBJECTIVE
Clozapine is a potent antipsychotic medication with a complex receptor profile. It is reserved for treatment-resistant schizophrenia. We systematically reviewed studies of non-psychosis symptoms of clozapine withdrawal.
METHODS
CINAHL, Medline, PsycINFO, PubMed, and the Cochrane Database of Systematic Reviews were searched using the keywords 'clozapine,' and 'withdrawal,' or 'supersensitivity,' 'cessation,' 'rebound,' or 'discontinuation'. Studies related to non-psychosis symptoms after clozapine withdrawal were included.
RESULTS
Five original studies and 63 case reports / series were included in analysis. In 195 patients included in the five original studies, approximately 20% experienced non-psychosis symptoms following discontinuation of clozapine. In 89 patients in four of the studies, 27 experienced cholinergic rebound, 13 exhibited extrapyramidal symptoms (including tardive dyskinesia), and three had catatonia. In 63 case reports / series included, 72 patients with non-psychosis symptoms were reported, which were catatonia (n=30), dystonia or dyskinesia (n=17), cholinergic rebound (n=11), serotonin syndrome (n=4), mania (n=3), insomnia (n=3), neuroleptic malignant syndrome (NMS) [n=3, one of them had both catatonia and NMS], and de novo obsessive compulsive symptoms (n=2). Restarting clozapine appeared to be the most effective treatment.
CONCLUSIONS
Non-psychosis symptoms following clozapine withdrawal have important clinical implications. Clinicians should be aware of the possible presentations of symptoms to ensure early recognition and management. Further research is warranted to better characterise the prevalence, risk factors, prognosis, and optimal drug dosing for each withdrawal symptom.
Topics: Humans; Antipsychotic Agents; Catatonia; Cholinergic Agents; Clozapine; Schizophrenia; Substance Withdrawal Syndrome
PubMed: 37400227
DOI: 10.12809/eaap2261 -
Frontiers in Pharmacology 2023Ondansetron is a selective antagonist of the serotonin 5-HT3 receptor that is commonly used to treat morning sickness. It is estimated that 70%-80% of pregnant women...
Ondansetron is a selective antagonist of the serotonin 5-HT3 receptor that is commonly used to treat morning sickness. It is estimated that 70%-80% of pregnant women suffer from morning sickness, a condition characterized by nausea and vomiting. However, it is still controversial regarding its safety during pregnancy, and continued research will be necessary to fully understand the risks and benefits associated with its use. Therefore, we aimed to identify and provide details of the efficacy and safety of ondansetron in clinical trials. A search was conducted of the ClinicalTrials.gov database on 13 April 2023, using the search term "ondansetron and pregnancy." Inclusion and exclusion criteria were defined to identify relevant clinical trials. The inclusion criteria encompassed clinical trials related to pregnancy that utilized ondansetron as a treatment, while other clinical trials were excluded from consideration. All data extractions such as study title, study status, study type, intervention details, and outcome were collected. A total of 18 clinical trials were identified, of which only 6 focused on studying the effects of ondansetron. Their respective study titles, statuses, conditions, interventions, outcome measures, and enrollment sizes have been written in detail. The information collected from these trials will contribute to our understanding of the potential benefits and risks of ondansetron in the context of pregnancy and its complications. Ondansetron has been shown to be an effective treatment for nausea and vomiting, including pregnancy-related morning sickness. Further research is needed to better understand the potential risks and benefits associated with its use in pregnant women. ClinicalTrials.gov, identifier.
PubMed: 37936910
DOI: 10.3389/fphar.2023.1291235 -
Diseases (Basel, Switzerland) Dec 2022There is growing evidence of the association of Microscopic Colitis (MC) with the use of specific medications such as proton pump inhibitors (PPIs), Selective serotonin...
There is growing evidence of the association of Microscopic Colitis (MC) with the use of specific medications such as proton pump inhibitors (PPIs), Selective serotonin reuptake inhibitors (SSRIs), Non-Steroidal anti-inflammatory drugs (NSAIDs), Statins and H2-receptor antagonists (H2RA). In our study, we calculated the pooled odds of MC in patients using these drugs. We performed a detailed search of major databases, including PubMed/Medline, Scopus, web of science, and Embase, to include the studies in which odds of MC were reported after using above mentioned drugs. A random-effects model was used to pool the estimates. Thirteen studies were included in our analysis consisting of 304,482 patients (34,194 cases and 270,018 controls). In eight studies, the control group consisted of a random population selected based on age, gender and same birth year, whereas 3 studies recruited patients who presented with diarrhea and underwent colonoscopy and biopsy to rule out MC. Two studies reported odds of MC for both diarrhea and random control groups. Patients taking PPIs were more likely to develop MC, AOR 2.65 (95% CI 1.81-3.50, 98.13%). Similarly, higher odds of association were found in patients taking SSRIs (OR 2.12, 95% CI 1.27-2.96, 96.46%), NSAIDs (OR 2.02, 95% CI 1.33-2.70, 92.70%) and Statins (OR 1.74, 95% CI 1.19-2.30, 96.36%). No difference in odds of developing MC was seen in patients using H2RA compared to the control group (OR 2.70, 95% CI 0.32-5.08, 98.67%). We performed a subgroup analysis based on the control group and found higher odds of MC in patients on PPIs compared to the random control group (OR 4.55, 95% CI 2.90-6.19, 98.13%). Similarly, higher odds of MC were noted for SSRI (OR 3.23, 95% CI 1.54-4.92, 98.31%), NSAIDs (OR 3.27, 95% CI 2.06-4.48, 95.38%), and Statins (OR 2.23, 95% CI 1.41-3.06, 98.11%) compared to the random control group. Contrary lower odds of MC were seen in the PPI and H2RA group compared to the diarrhea control group (OR 0.68, 95% CI 0.48-0.88, 7.26%), (OR 0.46, 95% CI 0.14-0.78, 0%) respectively. We found no difference in odds of MC in patients on SSRIs (OR 0.96, 95% CI 0.49-1.42, 37.89%), NSAIDs (OR 1.13, 95% CI 0.49-1.76, 59.37%) Statins (OR 0.91, 95% 0.66-1.17, 0%) and H2RA (OR 3.48, 95% CI -0.41-7.36, 98.89%) compared to the diarrhea control group. We also analyzed the association use of PPIs and NSAIDs with the development of collagenous colitis (CC) and lymphocytic colitis. Only the use of NSAIDs was associated with increased odds of developing collagenous colitis (OR 1.61, 95% CI 1.50-1.72, 0%). No increased odds of CC and LC were seen in PPI users. PPIs, NSAIDs, SSRIs, and Statins are associated with an increased risk of MC compared to the random control group. On the contrary, the use of PPIs, NSAIDs, SSRIs, and Statins is not associated with an increased risk of MC when compared to the diarrhea control group.
PubMed: 36648871
DOI: 10.3390/diseases11010006 -
Neuroscience and Biobehavioral Reviews Aug 2022The serotonergic system is involved in diverse cognitive functions including memory. Of particular importance to daily life are declarative memories that contain... (Review)
Review
The serotonergic system is involved in diverse cognitive functions including memory. Of particular importance to daily life are declarative memories that contain information about personal experiences, general facts, and events. Several psychiatric or neurological diseases, such as depression, attention-deficit-hyperactivity disorder (ADHD), and dementia, show alterations in serotonergic signalling and attendant memory disorders. Nevertheless, understanding serotonergic neurotransmission and its influence on memory remained a challenge until today. In this systematic review, we summarize recent psychopharmacological studies in animals and humans from a psychological memory perspective, in consideration of task-specific requirements. This approach has the advantage that comparisons between serotonin (5-HT)-related neurochemical mechanisms and manipulations are each addressing specific mnemonic circuits. We conclude that applications of the same 5-HT-related treatments can differentially affect unrelated tasks of declarative memories. Moreover, the analysis of specific mnemonic phases (e.g., encoding vs. consolidation) reveals opposing impacts of increased or decreased 5-HT tones, with low 5-HT supporting spatial encoding but impairing the consolidation of objects and verbal memories. Promising targets for protein synthesis-dependent consolidation enhancements include 5-HT receptor agonists and 5-HT receptor antagonists, with the latter being of special interest for the treatment of age-related decline. Further implications are pointed out as base for the development of novel therapeutic targets for memory impairment of neuropsychiatric disorders.
Topics: Animals; Attention Deficit Disorder with Hyperactivity; Cognition; Humans; Memory; Memory Disorders; Serotonin
PubMed: 35691469
DOI: 10.1016/j.neubiorev.2022.104729 -
Indian Pediatrics Aug 2023Serotonin receptors 5-HT1B and 5-HT1D in the cerebral arteries are activated by the 5-hydroxytryptophan agonists (triptans) to relieve the discomfort associated with...
BACKGROUND
Serotonin receptors 5-HT1B and 5-HT1D in the cerebral arteries are activated by the 5-hydroxytryptophan agonists (triptans) to relieve the discomfort associated with migraines. Even though triptans are often used to treat acute migraines, there is some debate over their effectiveness.
OBJECTIVE
Our systematic review aimed to evaluate the effectiveness of triptans for acute treatment of migraine in young individuals.
METHODS
Utilizing the databases of Google Scholar, Cochrane Library, and PubMed, a literature search was conducted, and all papers published till July 2022 were included. This systematic review was carried out following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. In addition to the Boolean operators AND, OR, and NOT, the following descriptive terms were also used: "Triptans," "Pediatric Migraine," "Migraine disorders," "Headache," "Children," and "Adolescent."
RESULTS
A total of 1047 studies were identified, and 25 articles were finally included in the study. 17 of them were RCTs while the remaining were non-randomized trials. Most studies recruited participants aged between 12-17 years. Among 25 studies, 7 reported sumatriptan use, 3 assessed a combination of sumatriptan and naproxen, 4 were on almotriptan, 1 on eletriptan, 6 on rizatriptan, and 4 on zolmitriptan use.
CONCLUSION
We found that rizatriptan (good tolerability profile with a dose of 5 mg) and sumatriptan (nasal spray, 10 mg and 20 mg) had higher efficiency as compared to other triptans. Regardless of type or dose, all triptans are generally well tolerated by patients, but a few adverse effects such as light-headedness (sumatriptan), nasopharyngitis, and, muscular spasms (sumatriptan/ naproxen), somnolence, and dry mouth (rizatriptan), and dizziness (zolmitriptan group) were reported with the triptans.
Topics: Adolescent; Humans; Child; Sumatriptan; Naproxen; Tryptamines; Migraine Disorders; Headache
PubMed: 37209053
DOI: No ID Found -
Pharmacology, Biochemistry, and Behavior Feb 2023Approximately two-thirds of patients with major depressive disorder (MDD) fail to respond to conventional antidepressants, suggesting that additional mechanisms are... (Review)
Review
Approximately two-thirds of patients with major depressive disorder (MDD) fail to respond to conventional antidepressants, suggesting that additional mechanisms are involved in the MDD pathophysiology. In this scenario, the glutamatergic system represents a promising therapeutic target for treatment-resistant depression. To our knowledge, this is the first study using semantic approach with systems biology to identify potential targets involved in the fast-acting antidepressant effects of ketamine and its enantiomers as well as identifying specific targets of (R)-ketamine. We performed a systematic review, followed by a semantic analysis and functional gene enrichment to identify the main biological processes involved in the therapeutic effects of these agents. Protein-protein interaction networks were constructed, and the genes exclusively regulated by (R)-ketamine were explored. We found that the regulation of α-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid (AMPA) receptor and N-methyl-d-aspartate (NMDA) receptor subunits-Postsynaptic Protein 95 (PSD-95), Brain Derived Neurotrophic Factor (BDNF), and Tyrosine Receptor Kinase B (TrkB) are shared by the three-antidepressant agents, reinforcing the central role of the glutamatergic system and neurogenesis on its therapeutic effects. Differential regulation of Transforming Growth Factor Beta 1 (TGF-β1) receptors-Mitogen-Activated Protein Kinases (MAPK's), Receptor Activator of Nuclear Factor-Kappa Beta Ligand (RANKL), and Serotonin Transporter (SERT) seems to be particularly involved in (R)-ketamine antidepressant effects. Our data helps further studies investigating the relationship between these targets and the mechanisms of (R)-ketamine and searching for other therapeutic compounds that share the regulation of these specific biomolecules. Ultimately, this study could contribute to improve the fast management of depressive-like symptoms with less detrimental side effects than ketamine and (S)-ketamine.
Topics: Humans; Ketamine; Depression; Depressive Disorder, Major; Systems Biology; Antidepressive Agents; Receptors, AMPA; Receptors, N-Methyl-D-Aspartate
PubMed: 36731751
DOI: 10.1016/j.pbb.2023.173523 -
Advances in Clinical and Experimental... Oct 2023Psychosis is a very common feature of Alzheimer's disease (AD) that can emerge as the neurodegenerative disease progresses. The 5-hydroxytryptamine (5-HT2A) receptors... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of negative allosteric modulators of 5-hydroxytryptamine 2A receptors in the treatment of Alzheimer's disease psychosis: A systematic review and meta-analysis.
BACKGROUND
Psychosis is a very common feature of Alzheimer's disease (AD) that can emerge as the neurodegenerative disease progresses. The 5-hydroxytryptamine (5-HT2A) receptors are located postsynaptically to serotonergic neurons in the frontal cortex and mediate both excitatory and inhibitory neurotransmissions. However, the effectiveness and tolerance of negative modulators of 5-HT2A receptors in Alzheimer's disease psychosis (ADP) are uncertain.
OBJECTIVES
To detect the negative modulators of the 5-HT2A receptor as a cure for ADP.
MATERIAL AND METHODS
The primary outcome indicator was the total Neuropsychiatric Inventory (NPI) score. Other prognostic indicators included Mini-Mental State Examination (MMSE), the Katz Index of Independence in Activities of Daily Living (KATZ), the discontinuation rate, and adverse events.
RESULTS
Compared to placebo, 5-HT2A inverse agonists significantly reduced the NPI total score, the KATZ and the MMSE score. The pooled odds ratio (OR) was 1.64 (95% confidence interval (95% CI): 1.01-2.65) and the heterogeneity variance was estimated at Tau2 = 0.52 with an I2 value of 90%, a χ2 value of 111.31, p = 0.04, and z-value of 2.01. The risk difference (RD) between the 5-HT2A receptor negative modulators and placebo groups was 0.12 (95% CI: 0.00-0.24) and the heterogeneity was estimated at Tau2 = 0.03, χ2 value of 127.23, degrees of freedom (df) value of 9, I2 value of 93%, z-value of 1.92, and p-value of 0.01 (<0.05).
CONCLUSION
Our results suggest that negative modulators of 5-HT2A receptors are beneficial and well-tolerated in the treatment of ADP.
Topics: Humans; Alzheimer Disease; Serotonin; Neurodegenerative Diseases; Activities of Daily Living; Drug Inverse Agonism; Receptor, Serotonin, 5-HT2A; Psychotic Disorders
PubMed: 37166012
DOI: 10.17219/acem/161159 -
Neuropsychopharmacology : Official... Mar 2022Ondansetron is a selective serotonin (5HT3) receptor antagonist that is under evaluation as an adjunctive treatment for schizophrenia, and a novel treatment for...
Ondansetron is a selective serotonin (5HT3) receptor antagonist that is under evaluation as an adjunctive treatment for schizophrenia, and a novel treatment for hallucinations in Parkinson's disease. Ondansetron reverses sensory gating deficits and improves visuoperceptual processing in animal models of psychosis, but it is unclear to what extent preclinical findings have been replicated in humans. We systematically reviewed human studies that evaluated the effects of ondansetron and other 5HT3 receptor antagonists on sensory gating deficits or sensory processing. Of 11 eligible studies, eight included patients with schizophrenia who were chronically stable on antipsychotic medication; five measured sensory gating using the P50 suppression response to a repeated auditory stimulus; others included tests of visuoperceptual function. Three studies in healthy participants included tests of visuoperceptual and sensorimotor function. A consistent and robust finding (five studies) was that ondansetron and tropisetron (5HT3 antagonist and α7-nicotinic receptor partial agonist) improved sensory gating in patients with schizophrenia. Tropisetron also improved sustained visual attention in non-smoking patients. There was inconsistent evidence of the effects of 5HT3 antagonists on other measures of sensory processing, but interpretation was limited by the small number of studies, methodological heterogeneity and the potential confounding effects of concomitant medication in patients. Despite these limitations, we found strong evidence that selective 5HT3 antagonists (with or without direct α7-nicotinic partial agonist effects) improved sensory gating. Future studies should investigate how this relates to potential improvement in neurocognitive symptoms in antipsychotic naive patients with prodromal or milder symptoms, in order to understand the clinical implications.
Topics: Antipsychotic Agents; Humans; Perception; Schizophrenia; Sensory Gating; alpha7 Nicotinic Acetylcholine Receptor
PubMed: 35017671
DOI: 10.1038/s41386-021-01255-4 -
Current Pain and Headache Reports Apr 2022Breast surgery is common and may result in significant acute as well as chronic pain. A wide range of pharmacologic interventions is available including opioids,... (Review)
Review
PURPOSE OF REVIEW
Breast surgery is common and may result in significant acute as well as chronic pain. A wide range of pharmacologic interventions is available including opioids, non-steroidal anti-inflammatory drugs (NSAIDs), N-methyl-D-aspartate (NMDA) receptor antagonists, anticonvulsants, and other non-opioids with analgesic properties. We present a review of the evidence for these pharmacologic interventions. A literature search of the MEDLINE database was performed via PubMed with combined terms related to breast surgery, anesthesia, and analgesia. Articles were limited to randomized controlled trial (RCT) design, adult patients undergoing elective surgery on the breast (not including biopsy), and pharmacologic interventions only. Article titles and abstracts were screened, and risk of bias assessments were performed.
RECENT FINDINGS
The search strategy initially captured 7254 articles of which 60 articles met the full inclusion criteria. Articles were organized according to intervention: 6 opioid agonists, 14 NSAIDs and acetaminophen, 4 alpha-2 agonists, 7 NMDA receptor antagonists, 6 local anesthetics, 7 steroids, 15 anticonvulsants (one of which also discussed an NMDA antagonist), 1 antiarrhythmic, and 2 serotonin reuptake inhibitors (one of which also studied an anticonvulsant). A wide variety of medications is effective for perioperative breast analgesia, but results vary by agent and dose. The most efficacious are likely NSAIDs and anticonvulsants. Some agents may also decrease the incidence of chronic postoperative pain, including flurbiprofen, gabapentin, venlafaxine, and memantine. While many individual agents are well studied, optimal combinations of analgesic medications remain unclear.
Topics: Adult; Analgesia; Analgesics; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Anticonvulsants; Breast Neoplasms; Female; Humans; N-Methylaspartate; Pain, Postoperative
PubMed: 35195851
DOI: 10.1007/s11916-022-01031-z -
Obesity Reviews : An Official Journal... Nov 2023This systematic review collates studies of dietary or bariatric surgery interventions for obesity using positron emission tomography and single-photon emission computed... (Review)
Review
Effects of bariatric surgery and dietary interventions for obesity on brain neurotransmitter systems and metabolism: A systematic review of positron emission tomography (PET) and single-photon emission computed tomography (SPECT) studies.
This systematic review collates studies of dietary or bariatric surgery interventions for obesity using positron emission tomography and single-photon emission computed tomography. Of 604 publications identified, 22 met inclusion criteria. Twelve studies assessed bariatric surgery (seven gastric bypass, five gastric bypass/sleeve gastrectomy), and ten dietary interventions (six low-calorie diet, three very low-calorie diet, one prolonged fasting). Thirteen studies examined neurotransmitter systems (six used tracers for dopamine DRD2/3 receptors: two each for C-raclopride, F-fallypride, I-IBZM; one for dopamine transporter, I-FP-CIT; one used tracer for serotonin 5-HT receptor, F-altanserin; two used tracers for serotonin transporter, C-DASB or I-FP-CIT; two used tracer for μ-opioid receptor, C-carfentanil; one used tracer for noradrenaline transporter, C-MRB); seven studies assessed glucose uptake using F-fluorodeoxyglucose; four studies assessed regional cerebral blood flow using O-H O (one study also used arterial spin labeling); and two studies measured fatty acid uptake using F-FTHA and one using C-palmitate. The review summarizes findings and correlations with clinical outcomes, eating behavior, and mechanistic mediators. The small number of studies using each tracer and intervention, lack of dietary intervention control groups in any surgical studies, heterogeneity in time since intervention and degree of weight loss, and small sample sizes hindered the drawing of robust conclusions across studies.
Topics: Humans; Positron-Emission Tomography; Tomography, Emission-Computed, Single-Photon; Bariatric Surgery; Brain; Obesity; Neurotransmitter Agents
PubMed: 37699864
DOI: 10.1111/obr.13620