Risks of Antidepressant induced psychotic events in patients with depression and psychosis

The aim of this ‘literature review’-based argumentative paper has been to find out the risks of developing psychotic and depressive disorders in patients having been treated with antidepressants. In order to reach a resounding supposition, this literature review-based argumentative study had taken an incisive look into previous research works and meta-analysis, which in effect had underscored the risks of antidepressant-induced psychotic and depressive disorders in patients with depression as well as psychosis even as the protagonists of antidepressant drug classes could not be undermined given their upscaled magnitude of benefits. While following a probing interpretation of past studies, this might be demystified that antidepressants could lead to psychotic events and depressive disorders in patients of all age groups with children and young adults being more susceptible to develop psychosis. The psychotic episodes could even be developed during initial phase of treatments in patients suffering from depressive and psychotic disorders such as bipolar mood disorder, unipolar depression, major depressive disorders, mania, OCD (Obsessive Compulsive Disorder), delusional depression (psychotic depression), schizophrenia, schizoaffective disorders alongside multiple somatic symptoms among others as well. Concomitantly, with efficaciousness of antidepressants in major depressive disorder still remaining a subject to utter dubitability, different antidepressant drug classes were found to be associated with a considerable scale of adverse effects after carrying out protracted arguments on findings of evidence-based past studies, meta-analysis of previous researches and relevant clinical cases. Therefore, following a systematized approach towards past studies, this argumentative research has reached a coherent conclusion that antidepressants are likely to cause psychotic events and exaggeration of depressive disorders up to some extent in several cases. Hence, there is a stipulation of individual risk-benefit assessment and intricate history taking in patients being contemplated for antidepressant drugs alongside a close observation and follow-up in patients of all age groups after introducing antidepressant medications.

Adverse Drug Reaction Monitoring of Antidepressant Drugs in a Mental Health Institute in Odisha

Introduction: Antidepressants are used primarily in the management of depressive and anxiety disorders. The occurrence of adverse drug reactions (ADRs) to antidepressants is a major challenge as it influences patient compliance. Aim: The aim of this study was to find out the ADR profile of antidepressant drugs in a mental health institute in Odisha. Materials and Methods: This is a cross sectional observational study conducted in Department of Pharmacology in collaboration with Mental Health Institute (Centre of Excellence) S.C.B Medical College and Hospital, Cuttack from September 2017 to September 2019. Patients who received at least one antidepressant drug were included in the study irrespective of age and sex. Data were collected by interviewing the patients or attendants and on detection of ADR, it was recorded on suspected ADR reporting form designed by PvPI. Causality, severity and preventability of ADRs were assessed by, WHO-UMC causality assessment, modified Hartwig-Siegel Scale and modified Schumock-Thornton criteria respectively. Results: Out of 180 patients taking antidepressants, ADRs were reported in 24% of patients, with either possible or probable causality. None were labelled as certain. ADRs were observed in 50% of patients who received TCAs and among 34.5% who received polytherapy. Insomnia (27%), fatigue (17%) and agitation (13%) were most common ADRs. Most of the ADRs were of mild severity (91%) and not preventable (84%). Conclusion: Insomnia, fatigue and agitation were among most common ADRs. There was increased chance of ADRs with polytherapy and use of TCAs. Most ADRs were mild and not preventable.

Design, Synthesis, and Antidepressant Activity Study of Novel Aryl Piperazines Targeting Both 5-HT1A and Sigma-1 Receptors

A total of 20 novel aryl piperazine derivatives were designed and synthesized, and their structures were confirmed by mass spectrometry and nuclear magnetic resonance analyses. Their 5-HT1A and sigma-1 receptor affinities were determined, and six of them showed high affinities (K i < 20 nmol/L) to both 5-HT1A and sigma-1 targets. Then, metabolic stability (T 1/2) tests of six compounds in rat and human liver microsomes were performed. Our data indicated that compound 27 has both high affinity for 5-HT1A and sigma-1 receptors (5-HT1A: K i = 0.44 nmol/L; sigma-1: K i = 0.27 nmol/L), and good metabolic stability (T 1/2 values are 21.7 and 24.6 minutes, respectively). Interestingly, results from the forced swimming test, mouse tail suspension test, and preliminary pharmacokinetic test suggested the marked antidepressant activity, good pharmacokinetic characteristics, and low toxicity of compound 27 in the two models. In conclusion, compound 27 has great value of further study as an active molecule of antidepressant drugs.

Antidepressant Use and Risk of Suicidal Behavior in Older Persons With Depression: A Cohort Study in Hong Kong

Background Depression is highly prevalent in older adults and requires treatment. However, debate persists on whether antidepressant use is associated with an elevated risk of suicidal behavior. This study aims to examine the short- and long-term risk of suicidal behavior by various classes of antidepressants in older persons with depression. Methods Persons aged 40 years and above and received a clinical diagnosis of depression between January 1, 2001, and December 31, 2016 were identified from the Clinical Data Analysis and Reporting System in Hong Kong. The risk of suicidal behavior in persons who were prescribed antidepressants was compared with persons who were not prescribed any antidepressant drugs. Antidepressants were classified as tricyclic and related antidepressant drugs (TCAs), selective serotonin reuptake inhibitors (SSRIs), noradrenergic and specific serotonergic antidepressants (NaSSAs), serotonin–norepinephrine reuptake inhibitors (SNRIs) and others. Incidence and adjusted hazard ratio (aHR) of subsequent self-harm and suicide within one-year and the whole study period were estimated by age groups. Results A total of 34,927 persons aged 40-64 years, and 19,300 persons aged 65+ years were included. In the younger age group, the highest short-term and long-term risks were found in others (aHR, 2.33; 1.02-5.34) and NaSSAs (2.88; 2.15-3.86), respectively. In the older age group, no significant association was observed between antidepressant use and suicidal behavior across all antidepressant classes. Conclusion The self-harm and suicide associated risks vary across antidepressant classes and age groups. Cautions are always needed for antidepressant prescriptions.

Chinese Pharmacopoeia Revisited: A Review of Anti-Depression Herbal Sources

Depression, which can be accompanied by many fatal diseases and a low life quality, has become the leading cause of ill health and disability worldwide. However, Chinese Pharmacopoeia, the most authoritative and evidence-based encyclopedia of Traditional Chinese Medicine (TCM), could contain leads and insights into the development of new antidepressant drugs. In this work, nine herbal medicines with ‘dispel melancholy functions’ specifically documented in Chinese Pharmacopoeia have been comprehensively reviewed with respect to clinical trials, and phytochemical and pharmacological aspects. The nine drugs are Rosae Chinensis Flos, Croci Stigma, Albiziae Cortex and Flos, Roase Rugosae Flos, Curcumae Radix, Hyperici Perforati Herba, Cyperi Rhizoma and Bupleuri Radix. The mechanisms of action of their functional antidepressant compounds, including gallic acid, hypericin, kaempferol, crocetin, crocin, quercetin, luteolin, isorhamnetin, curcumin, hyperforin, adhyperforin, catechin, rutin, puerarin, and saikosaponins A and D, have been collected and discussed. These traditional Chinese herbs and their active compounds provide a promising resource to develop effective new antidepressant drugs in future. Moreover, mechanistic investigations, safety verification and large-scale clinical trials are still expected to finally transform such TCM-based antidepressant resources to new drugs for patients suffering from depression.

Tryptophan Hydroxylase 2 Deficiency Modifies the Effects of Fluoxetine and Pargyline on the Behavior, 5-HT- and BDNF-Systems in the Brain of Zebrafish (Danio rerio)

The mechanisms of resistance to antidepressant drugs is a key and still unresolved problem of psychopharmacology. Serotonin (5-HT) and brain-derived neurotrophic factor (BDNF) play a key role in the therapeutic effect of many antidepressants. Tryptophan hydroxylase 2 (TPH2) is the rate-limiting enzyme in 5-HT synthesis in the brain. We used zebrafish (Danio rerio) as a promising model organism in order to elucidate the effect of TPH2 deficiency caused by p-chlorophenylalanine (pCPA) on the alterations in behavior and expression of 5-HT-related (Tph2, Slc6a4b, Mao, Htr1aa, Htr2aa) and BDNF-related (Creb, Bdnf, Ntrk2a, Ngfra) genes in the brain after prolonged treatment with two antidepressants, inhibitors of 5-HT reuptake (fluoxetine) and oxidation (pargyline). In one experiment, zebrafish were treated for 72 h with 0.2 mg/L fluoxetine, 2 mg/L pCPA, or the drugs combination. In another experiment, zebrafish were treated for 72 h with 0.5 mg/L pargyline, 2 mg/L pCPA, or the drugs combination. Behavior was studied in the novel tank diving test, mRNA levels were assayed by qPCR, 5-HT and its metabolite concentrations were measured by HPLC. The effects of interaction between pCPA and the drugs on zebrafish behavior were observed: pCPA attenuated “surface dwelling” induced by the drugs. Fluoxetine decreased mRNA levels of Tph2 and Htr2aa genes, while pargyline decreased mRNA levels of Slc6a4b and Htr1aa genes. Pargyline reduced Creb, Bdnf and Ntrk2a genes mRNA concentration only in the zebrafish treated with pCPA. The results show that the disruption of the TPH2 function can cause a refractory to antidepressant treatment.

Antidepressants and Circadian Rhythm: Exploring Their Bidirectional Interaction for the Treatment of Depression

Scientific evidence that circadian rhythms affect pharmacokinetics and pharmacodynamics has highlighted the importance of drug dosing-time. Circadian oscillations alter drug absorption, distribution, metabolism, and excretion (ADME) as well as intracellular signaling systems, target molecules (e.g., receptors, transporters, and enzymes), and gene transcription. Although several antidepressant drugs are clinically available, less than 50% of depressed patients respond to first-line pharmacological treatments. Chronotherapeutic approaches to enhance the effectiveness of antidepressants are not completely known. Even so, experimental results found until this day suggest a positive influence of drug dosing-time on the efficacy of depression therapy. On the other hand, antidepressants have also demonstrated to modulate circadian rhythmicity and sleep–wake cycles. This review aims to evidence the potential of chronotherapy to improve the efficacy and/or safety of antidepressants. It includes pre-clinical and clinical studies that demonstrate the relevance of determining the most appropriate time of administration for antidepressant drugs. In parallel, their positive influence on the resynchronization of disrupted circadian rhythms is also herein discussed. It is expected that this review will promote the investigation of chronotherapy for the treatment of depression, contribute to a better understanding of the relationship between antidepressants and circadian rhythms, and consequently promote the development of new therapeutics.