scholarly journals Possibilities and limitations of antidepressant use to correct depressive and negative symptoms in schizophrenia

2021 ◽  
Vol 1 (2) ◽  
pp. 21-45
Author(s):  
M. A. Novitsky ◽  
A. De Sousa ◽  
A. R. Asadullin ◽  
O. A. Gavrilyuk ◽  
A. V. Petrov ◽  
...  

The purpose of this review is to analyze approaches to the treatment of depressive and negative disorders in schizophrenia in terms of their level of efficacy and safety. Materials and Methods: A search was conducted for full-text articles published over the last 10 years in PubMed, Springer, Wiley Online Library, Taylor & Francis Online, APA PsycInfo, CORE, Science Direct, and eLIBRARY.RU databases. Several articles published previously to this period were also included into the review due to their high scientific value. Results: Our review suggests that antidepressants (ADs) are effective medications and they can be prescribed to correct depressive disorders and negative symptoms in patients with schizophrenia when used in combination with antipsychotics (АPs). However, when administering ADs and АPs combinations, it is important to consider the safety profile of these combinations as well as their tolerance. Negative symptoms of schizophrenia, including those induced by a number of АP, are less amenable to correction by АDs monotherapy, which requires a long period of АPs (on average - 8 weeks), which can be limited in the real life of the patient outside the hospital. Current approaches to the therapy of depressive disorders in patients suffering from schizophrenia vary from country to country. However, most of АDs used in clinical psychiatric practice are widely used in the comorbid state under consideration. Conclusion: The efficacy and safety of АDs of the different classes considered in this review depends on their mechanisms of action, duration of admission, type of АPs taken, and specific clinical situation (acute depressive disorder, major depressive episode, or chronic depressive episode). Most promising in clinical practice are serotonin–norepinephrine reuptake inhibitors (SNRIs) and dual ADs. The use of tricyclic antidepressants (TCAs) is limited due to a higher risk of adverse drug reactions (ADRs). The use of most selective serotonin reuptake inhibitors (SSRIs) is limited due to the risk of aggravation of hallucinations (this risk being higher for patients with visual hallucinations, and lower for those with auditory hallucinations) and\or iatrogenic psychosis. These ADRs may probably occur in patients suffering from schizophrenia due to their ideal "poor metabolizer" pharmacogenetic profile, since most of the drugs considered in this review have hepatic metabolism.

2018 ◽  
Vol 73 (6) ◽  
pp. 411-419 ◽  
Author(s):  
Mikhail S. Zastrozhin ◽  
Valery V. Smirnov ◽  
Alexander S. Sorokin ◽  
Elena A. Grishina ◽  
Kristina A. Ryzhikova ◽  
...  

Background: Alcohol dependence is often combined with affective disorders, in particular, depressive disorder (DD), which worsens adversely affects the prognosis of the course of both diseases and their outcomes. For the treatment of DD, drugs from the group of selective serotonin reuptake inhibitors, whose representative is fluvoxamine, are used. Fluvoxamine therapy is often associated with a risk of development is shown to be ineffective, and a part of patients develop dose-dependent adverse drug reactions (ADR) and pharmacoresistance.Objective: To study the effects of CYPD6 isoenzyme activity on the efficacy and safety of fluvoxamine therapy in patients with depressive disorders, comorbid with alcoholism.Methods: The study was conducted on 117 Russian patients with DD, alcohol-dependent comorbid. For the purpose of correction of depressive disorders within the framework of cyclothymia, fluvoxamine (Fevarin) was administered to patients at a dosage of 50−150 mg/day. Genotyping was carried out by the method of polymerase chain reaction in Real-time mode with allele-specific hybridization. Efficacy and safety were assessed using validated psychometric scales and an assessment of the severity of ADR. To evaluate the activity of CYP2D6, the method of high performance liquid chromatography with mass spectrometry was used to measure the urinary content of the endogenous substrate of this isoenzyme and its metabolite, the ratio of 6-hydroxy-1,2,3,4-tetrahydro-beta-carboline.Results: By the 9th day of the study, the severity of depressive symptoms on the HAMD scale was statistically significantly different in patients with different genotypes: (GG) 7.0 [6.0; 8.0], (GA) 4.0 [3.0; 5.0] (p0.001); safety indicator, estimated on a UKU scale: 3.0 [2.0; 4.0], (GA) 4.0 [4.0; 4.2] (p0.001). The presence of differences persisted on the 16th day: (GG) 5.0 [3.0; 6.0], (GA) 1.5 [1.0; 3.0] (p0.001); safety indicator, estimated on a UKU scale: (GG) 9.0 [9.0; 10.0], (GA) 6.0 [6.0; 7.0] (p0.001). The calculation of the correlation coefficients between the difference in the number of scores on psychometric scales and the metabolic ratio showed a statistically significant inverse correlation of the average power degree between the efficiency index estimated by the HAMD scale (r=-0.467, p0.05). There was no connection with the difference on the UKU scale (r=0.173, p0.05).Conclusion: In a study of a group of 117 patients with DD, comorbid with alcohol dependence, the effect of CYP2D6 activity, estimated by the ratio of the endogenous substrate concentrations of pinolin and its metabolite 6-hydroxy-1,2,3,4-tetrahydro-beta-carboline, on the efficacy of fluvoxamine therapy. This effect was also shown using the results of genotyping. The results of genotyping also showed the existence of a difference in the safety index in patients with different genotypes from the polymorphic marker CYP2D6 1846GA.


2021 ◽  
Vol 13 (3) ◽  
pp. 445-463
Author(s):  
Amber N. Edinoff ◽  
Juliana M. Fort ◽  
Joshua J. Woo ◽  
Christopher D. Causey ◽  
Caroline R. Burroughs ◽  
...  

The monoamine hypothesis of depression attributes the symptoms of major depressive disorders to imbalances of serotonin, noradrenaline, and dopamine in the limbic areas of the brain. The preferential targeting of serotonin receptor (SERT) by selective serotonin reuptake inhibitors (SSRIs) has offered an opportunity to reduce the range of these side effects and improve patient adherence to pharmacotherapy. Clozapine remains an effective drug against treatment-resistant schizophrenia, defined as failing treatment with at least two different antipsychotic medications. Patients with schizophrenia who display a constellation of negative symptoms respond poorly to antipsychotic monotherapy. Negative symptoms include the diminution of motivation, interest, or expression. Conversely to the depressive symptomology of interest presently, supplementation of antipsychotics with SSRIs in schizophrenic patients with negative symptoms lead to synergistic improvements in the function of these patients. Fluvoxamine is one of the most potent inhibitors of CYP1A2 and can lead to an increase in clozapine levels. Similar increases in serum clozapine were detected in two patients taking sertraline. However, studies have been contradictory as well, showing no such increases, which are worrying. Clinicians should be aware that clozapine levels should be monitored with any coadministration with SSRIs.


2016 ◽  
Vol 47 (1) ◽  
pp. 81-92 ◽  
Author(s):  
C.-S. Wu ◽  
S.-C. Liao ◽  
Y.-T. Tsai ◽  
S.-S. Chang ◽  
H.-J. Tsai

BackgroundThe aim of the study was to evaluate the comparative risk of self-harm associated with the use of different antidepressants.MethodA cohort study was conducted using data from Taiwan's National Health Insurance Research Database from 2001 to 2012. A total of 751 606 new antidepressant users with depressive disorders were included. The study outcome was hospitalization due to self-harm (International Classification of Diseases, Ninth Revision, Clinical Modification codes: E950–E958 and E980–E988). Cox proportional hazards models with stratification of the propensity score deciles were used to estimate the hazard ratios of self-harm hospitalization during the first year following the initiation of antidepressant treatment.ResultsThere were 1038 hospitalization episodes due to self-harm that occurred during the follow-up of 149 796 person-years, with an overall incidence rate of 6.9 [95% confidence interval (CI) 6.5–7.4] per 1000. Compared with fluoxetine, the risk of self-harm hospitalization was higher for maprotiline [adjusted hazard ratio (aHR) = 3.00, 95% CI 1.40–6.45], milnacipran (aHR = 2.34, 95% CI 1.24–4.43) and mirtazapine (aHR = 1.40, 95% CI 1.06–1.86), lower for bupropion (aHR = 0.51, 95% CI 0.30–0.86), and similar level of risk was found for other selective serotonin reuptake inhibitors (citalopram, escitalopram, fluvoxamine, paroxetine and sertraline).ConclusionsThe risk of self-harm may vary across different antidepressant drugs. It would be of importance to conduct further research to investigate the influence of antidepressant use on self-harm behaviors.


Author(s):  
Claudio Urbani ◽  
Francesca Dassie ◽  
Benedetta Zampetti ◽  
Di Certo Agostino Maria ◽  
Renato Cozzi ◽  
...  

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1485.3-1485
Author(s):  
F. Carubbi ◽  
A. Alunno ◽  
P. Cipriani ◽  
V. Pavlych ◽  
C. DI Muzio ◽  
...  

Background:Over the last 2 decades rituximab (RTX) has been widely used, albeit off-label, in primary Sjögren’s syndrome (pSS). Several studies reported that B-lymphocyte depletion with RTX is effective in this disease not only by reducing disease activity but also by affecting the inflammation and the lymphoid organization that occur in target tissues. With the recent release of several RTX biosimilars (bRTX) on the market, the demonstration of their interchangeability with RTX originator (oRTX) is required.Objectives:To compare efficacy and safety of oRTX and bRTX in pSS patients in a real-life setting.Methods:Clinical records of pSS patients referring to a tertiary rheumatology clinic were retrospectively evaluated. Patients having received at least 2 courses of either oRTX or bRTX (1000 mg IV infusion, repeated after 2 weeks -1 course- and the course repeated after 24 weeks) with complete data at baseline and after 3, 6, 9 and 12 months of treatment were enrolled. Disease activity was assessed with the EULAR SS disease activity index (ESSDAI) and its clinical version without the biological domain (ClinESSDAI). Patient-reported symptoms were assessed with the EULAR SS Patient Reported Index (ESSPRI).Results:Seven patients that received oRTX and 7 patients that received bRTX were enrolled. Baseline clinical features, including ESSDAI and ESSPRI were similar in the 2 treatment groups. Both compounds significantly reduced ESSDAI and ESSPRI as early as 3 months and no difference between the groups was observed at any time point (Figure 1). Of interest, ESSDAI slowly decreased until month 6 when the most pronounced reduction was observed. Conversely, ESSPRI dropped to its lowest values already at month 3. With regard to safety, at 12 months of follow-up no adverse event was observed in any of the treatment groups.Conclusion:At 12 months of follow-up, oRTX and bRTX display similar efficacy and safety profiles. The improvement of patient reported outcomes is faster than the improvement of disease activity with both compounds. Our data support interchangeability of oRTX and bRTX in pSS.References:[1]Carubbi F et al. Arthritis Res Ther. 2013;15(5):R172[2]Carubbi F et al. Lupus. 2014;23(13):1337-49Figure 1 ESSDAI and ESSPRI values at every time point in the 2 treatment groups. Asterisks indicate p values <0.05 compared to the other treatment group at the same time pointDisclosure of Interests:Francesco Carubbi Speakers bureau: Francesco Carubbi received speaker honoraria from Abbvie and Celgene outside this work., Alessia Alunno: None declared, Paola Cipriani Grant/research support from: Actelion, Pfizer, Speakers bureau: Actelion, Pfizer, Viktoriya Pavlych: None declared, claudia di muzio: None declared, Roberto Gerli: None declared, Roberto Giacomelli Grant/research support from: Actelion, Pfizer, Speakers bureau: Abbvie, Roche, Actelion, BMS, MSD, Ely Lilly, SOBI, Pfizer


2021 ◽  
Vol 9 (2) ◽  
pp. 26
Author(s):  
Narut Prasitlumkum ◽  
Wisit Cheungpasitporn ◽  
Nithi Tokavanich ◽  
Kimberly R. Ding ◽  
Jakrin Kewcharoen ◽  
...  

Background: Antidepressants are one of the most prescribed medications, particularly for patients with mental disorders. Nevertheless, there are still limited data regarding the risk of ventricular arrhythmia (VA) and sudden cardiac death (SCD) associated with these medications. Thus, we performed systemic review and meta-analysis to characterize the risks of VA and SCD among patients who used common antidepressants. Methods: A literature search for studies that reported risk of ventricular arrhythmias and sudden cardiac death in antidepressant use from MEDLINE, EMBASE, and Cochrane Database from inception through September 2020. A random-effects model network meta-analysis model was used to analyze the relation between antidepressants and VA/SCD. Surface Under Cumulative Ranking Curve (SUCRA) was used to rank the treatment for each outcome. Results: The mean study sample size was 355,158 subjects. Tricyclic antidepressant (TCA) patients were the least likely to develop ventricular arrhythmia events/sudden cardiac deaths at OR 0.24, 0.028–1.2, OR 0.32 (95% CI 0.038–1.6) for serotonin and norepinephrine reuptake inhibitors (SNRI), and OR 0.36 (95% CI 0.043, 1.8) for selective serotonin reuptake inhibitors (SSRI), respectively. According to SUCRA analysis, TCA was on a higher rank compared to SNRI and SSRI considering the risk of VA/SCD. Conclusion: Our network meta-analysis demonstrated the low risk of VA/SCD among patients using antidepressants for SNRI, SSRI and especially, TCA. Despite the relatively lowest VA/SCD in TCA, drug efficacy and other adverse effects should be taken into account in patients with mental disorders.


Sign in / Sign up

Export Citation Format

Share Document