Combination Of Antidepressants Research Articles

Understanding the potential of digital therapies in implementing the standard of care for depression in Europe.

Depressive disorders represent the largest proportion of mental illnesses, and by 2030, they are expected to be the first cause of disability-adjusted life years [1]. The COVID-19 pandemic exacerbated prevalence and burden of depression and increased the occurrence of depressive symptoms in general population [2]. The urgency of implementing mental health services to address new barriers to care persuaded clinicians to use telemedicine to follow patients and stay in touch with them, and to explore digital therapeutics (DTx) as potential tools for clinical intervention [2]. The combination of antidepressants and psychotherapy is widely recommended for depression by international guidelines [3] but is less frequently applied in real-world practice. Commonly used treatments are pharmacological, but while being effective, some aspects such as adherence to the drug regimen, residual symptoms, resistance, lack of information, and stigma may hinder successful treatment. In case of less severe depression, standalone psychological therapies should be the first-line treatment option [3], but access to trained psychotherapists remains inequitable. DTx are evidence-based therapies driven by software programs to treat or complement treatment of a specific disease. DTx are classified as Medical Devices, and given their therapeutic purpose, they need to be validated through randomized controlled clinical trials, as for drug-based therapies. In the last 10 years, studies of digital interventions have proliferated; these studies demonstrate that digital interventions increase remission rates and lower the severity of depressive symptoms compared with waitlist, treatment as usual, and attention control conditions [4]. Despite the efficacy demonstrated in clinical trials, many of these tools never reach real-life patients; thus, it might be necessary to implement DTx in the public health system to expand access to valid treatment options. In this framework, DTx represent a good opportunity to help people with depression receive optimal psychotherapeutic care [5].

TCA and SSRI Antidepressants Exert Selection Pressure for Efflux-Dependent Antibiotic Resistance Mechanisms in Escherichia coli.

Microbial diversity is reduced in the gut microbiota of animals and humans treated with selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs). The mechanisms driving the changes in microbial composition, while largely unknown, is critical to understand considering that the gut microbiota plays important roles in drug metabolism and brain function. Using Escherichia coli, we show that the SSRI fluoxetine and the TCA amitriptyline exert strong selection pressure for enhanced efflux activity of the AcrAB-TolC pump, a member of the resistance-nodulation-cell division (RND) superfamily of transporters. Sequencing spontaneous fluoxetine- and amitriptyline-resistant mutants revealed mutations in marR and lon, negative regulators of AcrAB-TolC expression. In line with the broad specificity of AcrAB-TolC pumps these mutants conferred resistance to several classes of antibiotics. We show that the converse also occurs, as spontaneous chloramphenicol-resistant mutants displayed cross-resistance to SSRIs and TCAs. Chemical-genomic screens identified deletions in marR and lon, confirming the results observed for the spontaneous resistant mutants. In addition, deletions in 35 genes with no known role in drug resistance were identified that conferred cross-resistance to antibiotics and several displayed enhanced efflux activities. These results indicate that combinations of specific antidepressants and antibiotics may have important effects when both are used simultaneously or successively as they can impose selection for common mechanisms of resistance. Our work suggests that selection for enhanced efflux activities is an important factor to consider in understanding the microbial diversity changes associated with antidepressant treatments. IMPORTANCE Antidepressants are prescribed broadly for psychiatric conditions to alter neuronal levels of synaptic neurotransmitters such as serotonin and norepinephrine. Two categories of antidepressants are selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs); both are among the most prescribed drugs in the United States. While it is well-established that antidepressants inhibit reuptake of neurotransmitters there is evidence that they also impact microbial diversity in the gastrointestinal tract. However, the mechanisms and therefore biological and clinical effects remain obscure. We demonstrate antidepressants may influence microbial diversity through strong selection for mutant bacteria with increased AcrAB-TolC activity, an efflux pump that removes antibiotics from cells. Furthermore, we identify a new group of genes that contribute to cross-resistance between antidepressants and antibiotics, several act by regulating efflux activity, underscoring overlapping mechanisms. Overall, this work provides new insights into bacterial responses to antidepressants important for understanding antidepressant treatment effects.

Meta-analysis overstates benefit of antidepressant combination therapy with α2-antagonists and reuptake inhibitors in major depression.

Meta-analysis overstates benefit of antidepressant combination therapy with α2-antagonists and reuptake inhibitors in major depression.

Characteristics of the treatments for each severity of major depressive disorder: A real-world multi-site study.

In the treatment guidelines for major depressive disorder (MDD), the recommended treatment differs based on the severity. However, the type of treatment provided based on the severity of MDD in real-world clinical practice has not been investigated. In this study, we clarified the actual situation of MDD treatment in clinical practice and compared the treatment based on the severity of MDD. We used data from 1484 patients with MDD at discharge from October 2016 to March 2020. The number of psychotropic prescriptions tended to be lower in those diagnosed with MDD in the severe group compared to in the non-severe group. There were significant differences among the three groups (mild, moderate/severe, and psychotic) in the percentage of patients who were not prescribed antipsychotics (p=1.9×10-6), a combination of antipsychotics and antidepressants (p=5.0×10-4), and the implementation rate of modified electroconvulsive therapy (m-ECT) (p=3.4×10-9). The percentage of patients with a severe diagnosis who underwent m-ECT was higher, which corresponded to the severity. Our findings showed that the use of psychotropics decreased when the severity of MDD was diagnosed, and the rate of a combination of antipsychotics and antidepressants and the implementation rate of m-ECT increased with the severity. However, this study suggests that there is still an evidence-practice gap in the treatment of MDD in Japan, and guidelines are only partially adhered to in the treatment of depression.

Safety and effectiveness of fixed dose combination of amitriptyline and chlordiazepoxide (Libotryp® and Libotryp-DS®) in the management of depression with co-morbid anxiety: protocol and design of a prospective, single arm, multi-centric, PMS study

<p><strong>Background:</strong> Depression and anxiety are most disabling psychiatric conditions and add significantly to global health-related burden. Lifetime prevalence of major depression and anxiety disorders are very common and many times they can co-exist in the same time frame. The outcomes are poorer in such situations and compliance to medication is key to improve prognosis. A combination of tricyclic antidepressants and benzodiazepine is more practical in terms of compliance, and advantageous than that of a single class of drugs for the management of depression with co-morbid anxiety. This study will evaluate the safety and effectiveness of a fixed dose combination of amitriptyline and chlordiazepoxide as a part of post marketing surveillance.</p><p><strong>Methods:</strong> This is a prospective, single-arm, multi-centre, study which enrols patients who have been initiated with FDC of amitriptyline and chlordiazepoxide (Libotryp<sup>®</sup>: amitriptyline 12.5 mg and chlordiazepoxide 5 mg or libotryp-DS<sup>®</sup>: amitriptyline 25 mg and chlordiazepoxide 10 mg) tablets for the treatment of depression with co-morbid anxiety. A total of 375 patients will be enrolled and clinical assessments for safety will be done at follow up visits; assessments for effectiveness will be done using Hamilton Depression Rating Scale (HDRS or HAM-D) and Hamilton Anxiety Rating Scale (HARS or HAM-A).</p><p><strong>Conclusions:</strong> This study will provide more evidence on safety and usefulness of FDC of amitriptyline and chlordiazepoxide for the treatment of depression with co-morbid anxiety from Indian context.</p><p><strong>Trial registration:</strong> Trial registration number is CTRI/2021/03/031971.</p>

Persistence of suicidal ideation within acute phase treatment of major depressive disorder: analysis of clinical predictors.

Suicidal ideation (SI) is common in major depressive disorder (MDD), and it is a risk factor for suicidal behaviour. Antidepressants are effective in reducing SI, but in some subjects, SI may persist for weeks. This study aimed to disentangle the contribution of baseline clinical characteristics in SI nonremission at week 6. Research involved 198 outpatients with MDD and SI collected within the Combining Medications to Enhance Depression Outcomes trial and treated with different antidepressant combinations. Although SI decreased from baseline to week 6 ( P < 0.0001), 78 patients (39%) failed to achieve SI remission. Insomnia [OR, 0.72; 95% confidence interval (CI), 0.52-0.99], reduced need for sleep (OR, 0.75; 95% CI, 0.58-0.99), self-confidence (OR, 0.52; 95% CI, 0.32-0.82), cheerfulness (OR, 0.57; 95% CI, 0.33-0.98), and comorbid panic disorder (OR, 0.93; 95% CI, 0.87-0.99) at baseline were associated with lack of SI remission after controlling for baseline depression and SI scores. The combination of baseline SI and insomnia was moderately effective in predicting the lack of SI remission, with a specificity of 80% (95% CI, 72-87%) and an NPV of 68% (95% CI, 63-72%). In individuals with MDD and SI, the presence of insomnia and bipolar features should prompt a search for more effective treatment solutions in order to favour SI remission and prevent suicidal behaviour.

Effects of Concomitant Benzodiazepines and Antidepressants Long-Term Use on Social Decision-Making: Results From the Ultimatum Game.

Benzodiazepines and antidepressants have been shown to change responses to unfairness; however, the effects of their combined use on unfairness evaluation are unknown. This study examines the effects of concomitant benzodiazepines and antidepressants long-term use on the evaluation of fair and unfair offers. To analyze behavioral changes on responses to unfairness, we compared the performance of medicated participants and healthy controls in the Ultimatum Game (UG), both in the proposer and in the respondent role. The results showed that long-term psychotropic users had the worse economic strategy by accepting less offers than control subjects. However, in the proposer role, the unfair offers made by participants were similar between groups. The present results suggest that long-term use of psychotropic medication, specifically the combination of benzodiazepines and antidepressants, may increase the sensitivity to unfairness, resulting in higher rejection rates in conditions where this strategy is the most disadvantageous.

Treatment-resistant Bipolar Disorder and Thyroid Cancer

IntroductionBipolar disorder (BD) is a chronic and recurrent illness frequently associated with functional deterioration and treatment challenges. High rates of thyroid dysfunction have been found in patients with BD, compared to the general population.ObjectivesTo illustrate through a case-report the therapeutic challenges of treatment-resistant bipolar disorder and its relationship with thyroid dysfunction.MethodsCase report of a 41-year-old male patient with BD and comorbid anxiety disorders who has been diagnosed with thyroid cancer and underwent total thyroidectomy.ResultsMr B is a 41 year old patient diagnosed with BD and comorbid anxiety disorders (panic disorder, social anxiety disorder and generalized anxiety disorder) at age 18. He has presented in total 17 relapses and was hospitalized 7 times between the ages of 18 and 24. He experienced predominantly major depressive episodes with mixed features and debilitating anxiety symptoms. He was put on several treatments including a combination of mood stabilizers, antidepressants and benzodiazepines. Due to unsatisfactory treatment response, he was put on clozapine 150mg to 175mg/d combined with valproic acid, clonazepam. In 2009, the patient developed a nodular goiter caused by papillary thyroid carcinoma and underwent total thyroidectomy and radioactive iodine therapy. Following the surgical operation and stabilization of thyroid functioning, a decrease in the number of relapses and the severity of mood and anxiety symptoms have been noted.ConclusionsThis case reports highlights the importance of thyroid function assessment in patients with bipolar disorder and the possible correlation to treatment resistance and symptom severity.DisclosureNo significant relationships.

Combination of clozapine, cariprazine and fluoxetine in treatment-resistant schizophrenia patient with prominent negative symptoms: A Case report

IntroductionDespite pharmacological advances in the treatment of schizophrenia, significant number of patients are still treatment-resistant. Clozapine is recommended as first-line treatment for treatment-resistant schizophrenia (TRS) in guidelines. Despite the greater efficacy of clozapine over other antipsychotics in the management of TRS, a significant number of patients fail to attain adequate response or develop adverse effects, and more interventions are needed.ObjectivesTo describe a clinical case of treatment-resistant schizophrenia patient with prominent negative symptoms treated with combination of clozapine, cariprazine and fluoxetine, and to review the literature.MethodsClinical case presentation through review of the clinical file and non-systematic review on PubMed and ResearchGate.ResultsA 41 year old female patient presented to inpatient clinic with low mood, occasional commanding and commenting verbal hallucinations, occasional suicidal thoughts, blunted affect, anhedonia, asociality, she was apathetic, lacked motivation to get up from bed, had night’s sleep disturbance. Patient was diagnosed with Schizophrenia in 2009, she has been hospitalized in Psychiatric wards for 16 times. She has received treatment with combinations of several antipsychotic drugs and antidepressants, had side-effects and have not reached full remission. During treatment with clozapine (up to 175mg per day) in combination with cariprazine (up to 4.5mg per day) and fluoxetine (up to 20mg per day), gradually negative symptoms decreased, patient became more active, showed interest in daily and rehabilitation activities, night’s sleep improved.Conclusions Patient with treatment-resistant schizophrenia benefited from combination of clozapine, cariprazine and fluoxetine. Further research is necessary on treatment combination strategies for TRS.DisclosureNo significant relationships.

Preliminary Evidence of Efficacy and Target Engagement of Pramipexole in Anhedonic Depression.

ObjectiveTo investigate feasibility and target engagement of high‐dose, add‐on pramipexole treatment in anhedonic depression.MethodIn this open‐label pilot study, we included 12 patients with unipolar or bipolar, moderate‐to‐severe depression and with significant anhedonia symptoms. All patients were on a stable dose of one or a combination of antidepressants and/or mood stabilizers and received 10 weeks of adjunctive pramipexole titrated to a maximum dose of 4.5 mg salt/day. All patients were rated with the Dimensional Anhedonia Rating Scale (DARS), the Montgomery Åsberg Depression Rating (MADRS) and the Snaith Hamilton Pleasure Scale (SHAPS). Serum high‐sensitivity C‐reactive protein (hs‐CRP) was analyzed pre‐ and post‐treatment. Eight patients underwent fMRI pre‐ and post‐treatment and a simplified version of the monetary incentive delay task was used to investigate the effect of treatment on striatal activity during reward anticipation.ResultsDARS, MADRS and SHAPS scores all improved significantly over 10 weeks of pramipexole treatment (p<0.01). Mean levels of hs‐CRP decreased significantly over the course of treatment from mean 3.8 mg/L at baseline to 2.6 mg/L at endpoint (p<0.01). There were significant treatment‐associated increases in reward related activity in several brain areas including the right lateral putamen, anterior left caudate, left posterior putamen, right dorsal caudate, left anterior putamen, and the right nucleus accumbens.ConclusionsThis is the first study to suggest efficacy and target engagement of pramipexole in anhedonic depression. Larger randomized controlled trials are needed to confirm or refute these preliminary findings.

Courses of treatment and risk factors for treatment-resistant depression in Finnish primary and special healthcare: A nationwide cohort study

ObjectiveInvestigate incidence, risk factors and courses of treatment for treatment-resistant depression (TRD) in primary and special healthcare. MethodsAll patients identified from nationwide registers, aged 16–65 years, diagnosed with depression in Finland during 2004–2016 were included. New antidepressant users were identified with six-month washout period and followed-up for two years to observe for presence of TRD, which was defined as initiation of a third trial after having failed two pharmacological treatment trials with adequate duration. ResultsDuring follow-up, 177,144 persons had their first registered antidepressant treated depression (mean age: 39.5, 62.5% women). Of them, 10.9% (N = 19,322) met TRD criteria. Among the TRD patients, most common first and second antidepressants trials were: SSRIs (44.6%), mirtazapine (19.0%) and SNRIs (16.5%). As the third treatment line, antidepressant monotherapy (44.2% of TRD patients) was most common, followed by a combination of ≥2 antidepressants (32.1%), antipsychotic or mood stabilizer augmentation and an antidepressant (15.8%), both combination of antidepressants and an augmentation with a mood stabilizer or antipsychotic (4.9%), antipsychotic or mood stabilizer monotherapy (2.7%) and ECT (0.3%). Of TRD patients, 16.5% (N = 3188) progressed to the fifth treatment line, in which the most common treatments were antidepressant monotherapy (33.4%), antidepressant combinations (27.5%) and augmentation (24.2%). Factors associated with higher risk of TRD included male gender, younger age, higher initial disease severity and hospitalization at initial onset of depression. ConclusionsAntidepressant monotherapies were still the most common fifth line of depression treatment. Severe depression, hospitalization due to depression, young age and male gender may predispose to TRD.

Drug-Induced Hyperprolactinemia and Hyponatremia - Biological Markers of Unfavorable Evolution in Schizophrenia

Adverse reactions to psychotropic medication can be considered as risk indicators for an unfavorable evolution of patients with schizophrenia, based on particular pathogenic mechanisms that can be used in the personalized therapeutic approach. The combination of antidepressants with antipsychotic drugs in schizophrenia has a risk of synergistic action of excessive blockade of dopamine receptors, which causes hyperprolactinemia. Primary hyponatremia occurs during pregnancy and can be an important marker for signaling neurodevelopmental abnormalities, while secondary hyponatremia has a major clinical dimension and is induced by psychotropic drugs. The pathogenic mechanisms presented can be objectified by neuroimaging examinations that bring benefits in the diagnostic accuracy and re-evaluation of the therapeutic approach, especially in correlation with the severity of biological markers such as prolactin and sodium. The persistence of high prolactin and low sodium levels is an alarm signal that announces a negative evolution of the patient or a major risk of severe cardiac, metabolic, vascular or renal comorbidities. Recognition of pathogenic mechanisms of neurodevelopment, including ventriculomegaly, hyponatremia, focal cortical dysplasia, hippocampal or temporal lobe lesions, in association with a positive history of neonatal or febrile seizures, requires prophylaxis due to high risk of onset of schizophrenia in childhood. Fetal cortical dysplasia is associated with the risk of neonatal seizures. This vulnerability favors the appearance of febrile convulsions or enuresis with changes in brain structure. Enuresis may be an important marker of neurodevelopmental potential for schizophrenia. Neonatal seizures are correlated with hyponatremia and severe hypertension, which appeared in the third trimester of pregnancy, can trigger eclampsia. Neuroimaging monitoring in patients with neurodevelopmental abnormalities, hyperprolactinemia and primary or secondary hyponatremia, acquires a major importance, being able to delimit the boundary between a functional lesion, potentially reversible, with an irreversible lesion.

Combining Antidepressants vs Antidepressant Monotherapy for Treatment of Patients With Acute Depression

Combining antidepressants is frequently done in the treatment of acute depression, but studies have yielded conflicting results. To conduct a systematic review and meta-analysis assessing efficacy and tolerability of combination therapy. Combinations using presynaptic α2-autoreceptor antagonists or bupropion were investigated separately. MEDLINE, Embase, PsycINFO, and the Cochrane Central Register of Controlled Trials were systematically searched from each database inception through January 2020. Randomized clinical trials (RCTs) comparing combinations of antidepressants with antidepressant monotherapy in adult patients with acute depression were included. Following guidelines from Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and recommendations from the Cochrane Handbook, 2 reviewers independently performed a literature search, study selection, data extraction, and evaluation of risk of bias. Data were pooled in random-effects analyses. Primary outcome was efficacy measured as standardized mean difference (SMD); secondary outcomes were response, remission, change from baseline in rating scale scores, number of dropouts, and number of dropouts due to adverse events. Thirty-nine RCTs including 6751 patients were eligible. Combination treatment was statistically significantly associated with superior treatment outcomes relative to monotherapy (SMD = 0.31; 95% CI, 0.19-0.44). Combining a reuptake inhibitor with an antagonist of presynaptic α2-autoreceptors was superior to other combinations (SMD = 0.37; 95% CI, 0.19-0.55). Bupropion combinations were not superior to monotherapy (SMD = 0.10; 95% CI, -0.07 to 0.27). Numbers of dropouts and dropouts due to adverse events did not differ between treatments. Studies were heterogeneous, and there was indication of publication bias (Egger test result was positive; P = .007, df = 36), but results remained robust across prespecified secondary outcomes and sensitivity and subgroup analyses, including analyses restricted to studies with low risk of bias. In this meta-analysis of RCTs comparing combinations of antidepressants with antidepressant monotherapy, combining antidepressants was associated with superior treatment outcomes but not with more patients dropping out of treatment. Combinations using an antagonist of presynaptic α2-autoreceptors may be preferable and may be applied as a first-line treatment in severe cases of depression and for patients considered nonresponders.

Medical Psychotropics in Forensic Autopsies in European Countries: Results from a Three-Year Retrospective Study in Spain.

Medical psychotropics are widely used and prescribed in developed countries. These medications may have an impairing effect on mood or perception and may induce harmful behaviors. Nevertheless, in Europe, studies on their importance from a medico-legal perspective are scarce. To fill this gap, we evaluate the determinants of these drugs in a retrospective study based on data obtained from forensic autopsies. Toxicological analyses were performed on 394 blood samples from compulsory autopsies at the Institute of Legal Medicine of Las Palmas. Of the samples, 41% (159) were positive for at least one psychotropic, with benzodiazepines being the most frequently detected (24.1%), followed by opiates and antidepressants. Benzodiazepines, opiates, and antidepressants were detected more frequently in men who suffered a violent death. More than 30% of the positive samples showed two or more drugs, suggesting a prevalence of polypharmacy among forensic autopsy subjects, with the most frequently combination found being benzodiazepines plus opiates (28.3% of positive samples). A combination of opiates plus antidepressants was also found in subjects involved in violent deaths. Our results suggest that more than 40% of the adult European population involved in medico-legal issues may be under the influence of legal psychotropics. The link between violent deaths and the use of medical psychotropics is particularly worrisome and indicates that these drugs should be carefully monitored in developed countries, in all forensic autopsies, in a similar way to illegal psychotropics.

Psychopharmacotherapy of late-stage hypochondriac conditions: frequency of use and effectiveness of drugs

To conduct a comparative analysis of psychopharmacotherapy effectiveness in hypochondriac disorders of late age and to identify the optimal combinations of drugs depending on the thymopathic (hypothymic and/or anxiety) components accompanying the main hypochondriac manifestation. One hundred and eight female inpatients, aged from 50 to 88 years, with leading hypochondriac symptoms of non-delusional level were enrolled in the study. All patients were examined clinically and psychopathologically using psychometric scales: the Montgomery-Asberg Depression Rating Scale, the Hamilton Anxiety Rating Scale, the hypochondria rating scale and the UKU side-effect rating scale. Based on the psychometric assessment, the patients were divided into the following groups: group 1 - subjects with hypochondriac symptoms without accented thymopathic component (n=18); group 2 - subjects with a high level of hypothymia (n=49); group 3 - subjects with a high level of anxiety (n=22); group 4 - subjects with a high level of both anxiety and depression (n=19). Hypochondriac disorder without a thymopathic component was treated with monotherapy with antipsychotic drugs in low therapeutic dosages or with a combination of antipsychotic drugs in low therapeutic dosages with tricyclic antidepressants in low and medium dosages. Hypothymic hypochondriac disorders were treated with antidepressants of mainly SSRIs group and of tricyclic structure in combination with typical and atypical antipsychotic drugs in low therapeutic dosages. In these patients monotherapy with antidepressants or a combination of different antidepressants was effective in rare cases only. Hypochondriac disorder with an anxiety component was significantly more often treated by complex therapy with the addition of anxiolytic drugs, as well as a combination of antidepressants with antiptychotic drugs. Mixed hypochondriac states were treated with a combination of antidepressants and antipsychotic drugs or complex therapy with the addition of an anxiolytic drug. Hypochondriac disorders of late age in most cases are accompanied by depressive and/or anxiety symptoms, which must be taken into account for improvement of diagnostic effectiveness and relevant selection of therapy.

Treatment aspects of youth depression with attenuated schizophrenic symptoms

To analyze main aspects of the treatment of patients with youth depression with attenuated schizophrenic symptoms (ASS). Two hundred and nineteen young in-patients (median age 19.6±2.4) with the first depressive episode (F32.1, F32.2, F32.38, F32.8.) and ASS were examined. The comparison group included 52 patients with depression without ASS with similar socio-demographic and age characteristics (average age 19.8±2.7 years). The efficacy of the therapy was assessed by the reduction of HDRS, SOPS and SANS scores. The Drug Compliance Scale was used to assess the compliance of patients. The average duration of in-patient treatment did not differ between groups (56.3 days in the main group and 54.2 days in the comparison group). The most effective therapy was found in the depression reduction on HDRS (67.9% and 76.6% respectively), the ASS reduction was 46.1% on the SOPS and 31.2% on the SANS. The combination of antidepressants (46.0±28.9 mg/day for fluoxetine equivalents) and antipsychotics (385.4±210.7 mg/day for chlorpromazine equivalents) were required to achieve this efficacy. The average duration of continued treatment was 7.4±9.6 months that was significantly lower (p<0.05) than in the comparison group (11.7±9.0 months), which was determined by the low compliance of such patients. The results show that a combination treatment and the implementation of measures, increasing the degree of compliance are required to increase the efficacy of treatment in patients with youth depression and ASS.

Combined treatment with mirtazapine linked to better outcomes in patients with acute depression, review shows

Combination therapy involving a presynaptic α2-autoreceptor antagonist, such as mirtazapine, may be an effective and safe treatment option for patients with severe depression, a systematic review and meta-analysis in JAMA Psychiatry has concluded. Published on 16 February 2022, the meta-analysis looked at 39 randomised clinical trials, comprising 6,751 patients, comparing combinations of antidepressants with antidepressant […]

Psychoemotional disorders in postmenopausal women and methods of their correction

Psycho-emotional disorders in postmenopausal women are caused by interaction of neuroendocrine changes, psychological and social factors. They include anxiety, depression, dissomnia,psychosexual and cognitive dysfunction. Hormonal replacement therapy is widely used in correction of psycho-emotional disturbances in postmenopausal women. Combination of estrogens and antidepressants appears to have good prospects.

Detailing the effects of polypharmacy in psychiatry: longitudinal study of 320 patients hospitalized for depression or schizophrenia

Current treatment standards in psychiatry are oriented towards polypharmacy, that is, patients receive combinations of several antidepressants, antipsychotics, mood stabilizers, anxiolytics, hypnotics, antihistamines, and anticholinergics, along with other somatic treatments. In tandem with the beneficial effects of psychopharmacological drug treatment, patients experience significant adverse reactions which appear to have become more frequent and more severe with the rise of ubiquitous polypharmacy. In this study, we aimed to assess today’s acute inpatient treatment of depressive and schizophrenic disorders with focus on therapeutic strategies, medications, adverse side effects, time course of recovery, and efficacy of treatments. Of particular interest was the weighing of the benefits and drawbacks of polypharmacy regimens. We recruited a total of 320 patients hospitalized at three residential mental health treatment centers with a diagnosis of either schizophrenic (ICD-10: “F2x.x”; n = 94; “F2 patients”) or depressive disorders (ICD-10: “F3x.x”; n = 226; “F3 patients”). The study protocol included (1) assessment of previous history by means of the SADS Syndrome Check List SSCL-16 (lifetime version); (2) repeated measurements over 5 weeks assessing the time course of improvement by the Hamilton Depression Scale HAM-D and the Positive and Negative Syndrome Scale PANSS, along with medications and adverse side effects through the Medication and Side Effects Inventory MEDIS; and (3) the collection of blood samples from which DNA and serum were extracted. Polypharmacy was by far the most common treatment regimen (85%) in this study. On average, patients received 4.50 ± 2.68 medications, consisting of 3.30 ± 1.84 psychotropic drugs, plus 0.79 ± 1.13 medications that alleviate adverse side effects, plus 0.41 ± 0.89 other somatic medications. The treating psychiatrists appeared to be the main determining factor in this context, while «previous history» and «severity at baseline» played a minor role, if at all. Adverse drug reactions were found to be an inherent component of polypharmacy and tended to have a 2–3 times higher incidence compared to monotherapy. Severe adverse reactions could not be attributed to a particular drug or drug combination. Rather, the empirical data suggested that severe side effects can be triggered by virtually all combinations of drugs, provided patients have a respective vulnerability. In terms of efficacy, there were no advantages of polypharmacy over monotherapy. The results of this study underlined the fact that polypharmacy regimens are not equally suited for every patient. Specifically, such regimens appeared to have a negative impact on treatment outcome and to obfuscate the “natural” time course of recovery through a multitude of interfering factors. Evidence clearly speaks against starting just every therapeutic intervention in psychiatry with a combination of psychopharmaceuticals. We think that it is time for psychiatry to reconsider its treatment strategies, which are far too one-sidedly fixated on psychopharmacology and pay far too little attention to alternative approaches, especially in mild cases where psychotherapy without concurrent medication should still be an option. Also, regular exercises and sports can definitely be an effective therapeutic means in a considerable number of cases. General practitioners (GPs) are particularly in demand here.

Evidence on sociodemographic and clinical correlates of antidepressant combination or augmentation with second-generation antipsychotics in major depressive disorder

About two thirds of the patients with major depressive disorder (MDD) do not sufficiently respond to monotherapy with antidepressants (ADs) which makes them reliant on further treatment approaches. Hereby, combination of different ADs and augmentation with second-generation antipsychotics (SGAs) are widely used and recommended psychopharmacotherapeutic strategies.The present secondary analyses are based on an international, naturalistic, cross-sectional multicenter study conducted by the European Group for the Study of Resistant Depression. Comparing socio-demographic and clinical characteristics of 436 adult MDD patients receiving either SGAs (N = 191, 43.8%) or ADs (N = 245, 56.2%), that were additionally administered to their first-line AD psychopharmacotherapy, we aimed to identify possible trajectories of decision-making for clinicians regarding which treatment option to prefer in individual patients.Our most robust findings represent an association of SGA augmentation with the presence of psychotic symptoms, longer mean duration of lifetime psychiatric hospitalizations, employment of further augmentation strategies with mood-stabilizers and benzodiazepines, and a trend towards higher mean daily dosages of their first-line ADs and current suicidal risk. Treatment outcome was not significantly different between patients receiving either SGA augmentation or AD combination.Being aware of limitations inherent to the cross-sectional study design and the lack of randomization, more severe and rather chronic conditions in MDD seemed to encourage clinicians to choose SGA augmentation over AD combination. The fact that mood-stabilizers and/or benzodiazepines were more frequently co-administered with SGAs may represent a requirement of an overall refined psychopharmacotherapy including additional fast-acting agents with potent AD, tranquilizing and anti-suicidal effects in MDD patients experiencing challenging clinical manifestations. New glutamatergic substances seem to be promising in this regard.