A network meta‐analysis of the effects of psychotherapies,pharmacotherapies and their combination in the treatment of adult depression

No network meta‐analysis has examined the relative effects of psychotherapies, pharmacotherapies and their combination in the treatment of adult depression, while this is a very important clinical issue. We conducted systematic searches in bibliographical databases to identify randomized trials in which a psychotherapy and a pharmacotherapy for the acute or long‐term treatment of depression were compared with each other, or in which the combination of a psychotherapy and a pharmacotherapy was compared with either one alone. The main outcome was treatment response (50% improvement between baseline and endpoint). Remission and acceptability (defined as study drop‐out for any reason) were also examined. Possible moderators that were assessed included chronic and treatment‐resistant depression and baseline severity of depression. Data were pooled as relative risk (RR) using a random‐effects model. A total of 101 studies with 11,910 patients were included. Depression in most studies was moderate to severe. In the network meta‐analysis, combined treatment was more effective than psychotherapy alone (RR=1.27; 95% CI: 1.14‐1.39) and pharmacotherapy alone (RR=1.25; 95% CI: 1.14‐1.37) in achieving response at the end of treatment. No significant difference was found between psychotherapy alone and pharmacotherapy alone (RR=0.99; 95% CI: 0.92‐1.08). Similar results were found for remission. Combined treatment (RR=1.23; 95% CI: 1.05‐1.45) and psychotherapy alone (RR=1.17; 95% CI: 1.02‐1.32) were more acceptable than pharmacotherapy. Results were similar for chronic and treatment‐resistant depression. The combination of psychotherapy and pharmacotherapy seems to be the best choice for patients with moderate depression. More research is needed on long‐term effects of treatments (including cost‐effectiveness), on the impact of specific pharmacological and non‐pharmacological approaches, and on the effects in specific populations of patients.     

Polyamine Oxidase Activity in Sera of Depressed and Schizophrenic Patients after ECT Treatment

High level of polyamine oxidase activity is detected in sera of depressed as well as in schizophrenic patients. ECT treatment of depressed and schizophrenic patients reduced significantly the level of polyamine oxidase activity in their sera. After ECT treatment, clinically improved depressed and schizophrenic subjects were found to have sera polyamine oxidase activity not significantly differ from that of normal subjects. Possible biochemical mechanisms, which link polyamine oxidase activity, schizophrenia, depression and ECT effect are discussed here.     

G protein signaling and the molecular basis of antidepressant action

Over the past four decades, a variety of interventions have been used for the treatment of clinical depression and other affective disorders. Several distinct pharmacological compounds show therapeutic efficacy. There are three major classes of antidepressant drugs: monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), and tricyclic compounds. There are also a variety of atypical antidepressant drugs, which defy ready classification. Finally, there is electroconvulsive therapy, ECT. All require chronic (2-3 weeks) treatment to achieve a clinical response. To date, no truly inclusive hypothesis concerning a mechanism of action for these diverse therapies has been formed. This review is intended to give an overview of research concerning G protein signaling and the molecular basis of antidepressant action. In it, the authors attempt to discuss progress that has been made in this arena as well as the possibility that some point (or points) along a G protein signaling cascade represent a molecular target for antidepressant therapy that might lead toward a unifying hypothesis for depression. This review is not designed to address the clinical studies. Furthermore, as it is a relatively short paper, citations to the literature are necessarily selective. The authors apologize in advance to authors whose work we have failed to cite.     

Adding psychotherapy to antidepressant medication in depression and anxiety disorders: a meta‐analysis

We conducted a meta‐analysis of randomized trials in which the effects of treatment with antidepressant medication were compared to the effects of combined pharmacotherapy and psychotherapy in adults with a diagnosed depressive or anxiety disorder. A total of 52 studies (with 3,623 patients) met inclusion criteria, 32 on depressive disorders and 21 on anxiety disorders (one on both depressive and anxiety disorders). The overall difference between pharmacotherapy and combined treatment was Hedges' g = 0.43 (95% CI: 0.31‐0.56), indicating a moderately large effect and clinically meaningful difference in favor of combined treatment, which corresponds to a number needed to treat (NNT) of 4.20. There was sufficient evidence that combined treatment is superior for major depression, panic disorder, and obsessive‐compulsive disorder (OCD). The effects of combined treatment compared with placebo only were about twice as large as those of pharmacotherapy compared with placebo only, underscoring the clinical advantage of combined treatment. The results also suggest that the effects of pharmacotherapy and those of psychotherapy are largely independent from each other, with both contributing about equally to the effects of combined treatment. We conclude that combined treatment appears to be more effective than treatment with antidepressant medication alone in major depression, panic disorder, and OCD. These effects remain strong and significant up to two years after treatment. Monotherapy with psychotropic medication may not constitute optimal care for common mental disorders.     

Repetitive transcranial magnetic stimulation (rTMS) in major depressive episode during pregnancy

Sir: For women diagnosed with Recurrent depressive disorder, pregnancy poses a major treatment challenge. Apart from antidepressants, the most commonly used biological therapeutical method is ECT (electroconvulsive therapy). We believe that similar efficacy can be achieved using rTMS as a safer option with substantially less side effects. So far, only a few case-reports reporting the use of rTMS for treatment of pregnant patients with depression were published.     

Repetitive transcranial magnetic stimulation induces kf-1 expression in the rat brain

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive approach used for stimulating the brain, and has proven effective in the treatment of depression, however the mechanism of its antidepressant action is unknown. Recently, we have reported the induction of kf-1 in rat frontal cortex and hippocampus after chronic antidepressant treatment and repeated electroconvulsive treatment (ECT). In this study, we demonstrated the induction of kf-1 after rTMS in the rat frontal cortex and hippocampus, but not in hypothalamus. Our data suggest that kf-1 may be a common functional molecule that is increased after antidepressant treatment, ECT and rTMS. In conclusion, it is proposed that induction of kf-1 may be associated with the treatment induced adaptive neural plasticity in the brain, which is a long-term target for their antidepressant action.     

Electroconvulsive Therapy Induces Neurogenesis in Frontal Rat Brain Areas

Electroconvulsive therapy (ECT) is an effective therapy for several psychiatric disorders, including severe major depression, mania and certain forms of schizophrenia. It had been proposed that ECT acts by modulating local plasticity via the stimulation of neurogenesis. In fact, among antidepressant therapies, ECT is the most robust enhancer of neurogenesis in the hippocampus of rodents and non-human primates. The existence of ECT-triggered neurogenesis in other brain areas, particularly in those adjacent to the other main locus of neurogenesis, the subventricular zone (SVZ), had so far remained unknown. Here we show that ECT also strongly enhances neurogenesis in frontal brain areas, especially in the rostro-medial striatum, generating specific, small-size calretinin-positive interneurons. We provide here the first evidence that ECT stimulates neurogenesis in areas outside the hippocampus. Our data may open research possibilities that focus on the plastic changes induced by ECT in frontal limbic circuitry.     

Abandoning personalization to get to precision in the pharmacotherapy of depression

Effectiveness studies and analyses of naturalistic cohorts demonstrate that many patients with major depressive disorder do not experience symptomatic remission with antidepressant treatments. In an effort to better match patients with effective treatments, numerous investigations of predictors or moderators of treatment response have been reported over the past five decades, including clinical features as well as biological measures. However, none of these have entered routine clinical practice; instead, clinicians typically personalize treatment on the basis of patient preferences as well as their own. Here, we review the reasons why it has been challenging to identify and deploy treatment‐specific predictors of response, and suggest strategies that may be required to achieve true precision in the pharmacotherapy of depression. We emphasize the need for changes in how depression care is delivered, measured, and used to inform future practice.     

Clinical Considerations Regarding the Use of Obesity Pharmacotherapy in Adolescents with Obesity

A growing number of youth suffer from obesity and in particular severe obesity for which intensive lifestyle intervention does not adequately reduce excess adiposity. A treatment gap exists wherein effective treatment options for an adolescent with severe obesity include intensive lifestyle modification or metabolic and bariatric surgery while the application of obesity pharmacotherapy remains largely underutilized. These youth often present with numerous obesity‐related comorbid diseases, including hypertension, dyslipidemia, prediabetes/type 2 diabetes, obstructive sleep apnea, nonalcoholic fatty liver disease, musculoskeletal problems, and psychosocial issues such as depression, anxiety, and social stigmatization. Current pediatric obesity treatment algorithms for pediatric primary care providers focus primarily on intensive lifestyle intervention with escalation of treatment intensity through four stages of intervention. Although a recent surge in the number of Food and Drug Administration‐approved medications for obesity treatment has emerged in adults, pharmacotherapy options for youth remain limited. Recognizing treatment and knowledge gaps related to pharmacological agents and the urgent need for more effective treatment strategies in this population, discussed here are the efficacy, safety, and clinical application of obesity pharmacotherapy in youth with obesity based on current literature. Legal ramifications, informed consent regulations, and appropriate off‐label use of these medications in pediatrics are included, focusing on prescribing practices and prescriber limits.     

Anorexia nervosa and bulimia nervosa.

No definitive therapy exists for anorexia nervosa (AN) or bulimia nervosa (BN). Nevertheless, biologic and psychologic research into these disorders has increased over the last decade. We examine the various drugs available for treatment. Advances in pharmacotherapy for AN have been modest and have reflected efforts either to stimulate hunger and weight gain or to control complications of the starvation process. Food remains the "drug" of choice. Antidepressants have been found to be beneficial in the treatment of BN. The meaning of this in the context of a relation between BN and mood disorders remains unclear, since coexistent depression does not predict a positive response to these drugs. Pharmacotherapy represents a single but important dimension of the management of patients with eating disorders. The optimal integration of drug therapy and psychotherapy and the identification of predictors of a positive response to drugs have yet to be addressed by clinical research.     

A prospective study of the psychobehavioral factors responsible for a change from non-patient irritable bowel syndrome to IBS patient status

Background

The literature measuring effects of antidepressant and electroconvulsive therapy (ECT) for major depression on heart rate variability (HRV) in medically well individuals was reviewed.

Methods

Fourteen studies evaluating HRV were included. Twenty three pre-post or within group comparisons were available. Treatment impact on measures of HRV was pooled over studies. We examined different classes of antidepressants, and for short and long electrocardiogram (ECG) recordings separately.

Results

Tricyclic antidepressants (TCAs) were associated with declines in most measures of HRV and significant increase in heart rate (HR) in studies with short recording intervals. No significant changes were found for longer recording times. Treatment effects with selective serotonin reuptake inhibitors (SSRIs) were more variable. Short-recording studies revealed a significant decrease in HR and an increase in one HRV measure. In two 24-hour recording studies no significant changes were observed. No relationship between ECT and HRV has been established in the literature. The effects of other drugs are reported.

Limitations

Few studies measure the effects of treatment of depression on HRV. Existing studies have generally used very small samples, employing a variety of measurements and methodologies.

Conclusion

We confirm that TCAs are associated with a large decrease in HRV and increase HR. However, data for SSRIs is not clear. Although the effect of SSRIs on HRV is weaker than for TCAs, evidence shows that SSRIs are associated with a small decrease in HR, and an increase in one measure of HRV. The use of TCAs in depression leads to changes in HRV that are associated with increased risk of mortality.     

Efficacy of light therapy for perinatal depression: a review

ABSTRACT: Perinatal depression is an important public health problem affecting 10-20% of childbearing women. Perinatal depression is associated with significant morbidity, and has enormous consequences for the well-being of the mother and child. Treatment of depression during the perinatal period poses a complex problem for both mother and clinician, as antidepressant treatment strategies must consider the welfare of both mother and child during pregnancy and lactation. Bright light therapy may be an attractive treatment for perinatal depression because it is low cost, home-based, and has a much lower side effect profile than pharmacotherapy. The antidepressant effects of bright light are well established, and there are several rationales for expecting that bright light might also be efficacious for perinatal depression. This review describes these rationales, summarizes the available evidence on the efficacy of bright light therapy for perinatal depression, and discusses future directions for investigation of bright light therapy as a treatment for perinatal depression.     

Antidepressant and Neurocognitive Effects of Isoflurane Anesthesia versus Electroconvulsive Therapy in Refractory Depression

Background

Many patients have serious depression that is nonresponsive to medications, but refuse electroconvulsive therapy (ECT). Early research suggested that isoflurane anesthesia may be an effective alternative to ECT. Subsequent studies altered drug, dose or number of treatments, and failed to replicate this success, halting research on isoflurane''s antidepressant effects for a decade. Our aim was to re-examine whether isoflurane has antidepressant effects comparable to ECT, with less adverse effects on cognition.

Method

Patients with medication-refractory depression received an average of 10 treatments of bifrontal ECT (n = 20) or isoflurane (n = 8) over 3 weeks. Depression severity (Hamilton Rating Scale for Depression-24) and neurocognitive responses (anterograde and retrograde memory, processing speed and verbal fluency) were assessed at Pretreatment, Post all treatments and 4-week Follow-up.

Results

Both treatments produced significant reductions in depression scores at Post-treatment and 4-week Follow-up; however, ECT had modestly better antidepressant effect at follow-up in severity-matched patients. Immediately Post-treatment, ECT (but not isoflurane) patients showed declines in memory, fluency, and processing speed. At Follow-up, only autobiographical memory remained below Pretreatment level for ECT patients, but isoflurane patients had greater test-retest neurocognitive score improvement.

Conclusions

Our data reconfirm that isoflurane has an antidepressant effect approaching ECT with less adverse neurocognitive effects, and reinforce the need for a larger clinical trial.     

Review. Evidence-based treatments of addiction

Both pharmacotherapy and behavioural treatment are required to relieve the symptoms of addictive disorders. This paper reviews the evidence for the benefits of pharmacotherapy and discusses mechanisms where possible. Animal models of addiction have led to some medications that are effective in reducing symptoms and improving function but they do not produce a cure. Addiction is a chronic disease that tends to recur when treatment is stopped; thus, long-term treatment is recommended.     

Perinatal depression: implications for child mental health

Perinatal depression is common and primary care holds a crucial role for detecting, treating or, if necessary, providing referrals to mental health care for affected women. Family doctors should be aware of risk factors for peripartum depression, including previous history of depression, life events and interpersonal conflict. Perinatal depression has been associated with many poor outcomes, including maternal, child and family unit challenges. Infants and young children of perinatally depressed mothers are more likely to have a difficult temperament, as well as cognitive and emotional delays. The primary care setting is uniquely poised to be the screening and treatment site for perinatal depression; however, several obstacles, both at patient and systems level, have been identified that interfere with women's treatment engagement. Current published treatment guidelines favour psychotherapy above medicines as first line treatment for mild to moderate perinatal depression, while pharmacotherapy is first choice for severe depression, often in combination with psychosocial or integrative approaches. Among mothers who decide to stop taking their antidepressants despite ongoing depression during the perinatal period, the majority suffer from relapsing symptoms. If depression continues post-partum, there is an increased risk of poor mother-infant attachment, delayed cognitive and linguistic skills in the infant, impaired emotional development and risk for behavioural problems in later life. Complex, comprehensive and multilevel algorithms are warranted to treat perinatal depression. Primary care doctors are best suited to initiate, carry out and evaluate the effectiveness of such interventions designed to prevent adverse outcomes of maternal perinatal depression on mother and child wellbeing.     

Planning of Electroporation-Based Treatments Using Web-Based Treatment-Planning Software

Electroporation-based treatment combining high-voltage electric pulses and poorly permanent cytotoxic drugs, i.e., electrochemotherapy (ECT), is currently used for treating superficial tumor nodules by following standard operating procedures. Besides ECT, another electroporation-based treatment, nonthermal irreversible electroporation (N-TIRE), is also efficient at ablating deep-seated tumors. To perform ECT or N-TIRE of deep-seated tumors, following standard operating procedures is not sufficient and patient-specific treatment planning is required for successful treatment. Treatment planning is required because of the use of individual long-needle electrodes and the diverse shape, size and location of deep-seated tumors. Many institutions that already perform ECT of superficial metastases could benefit from treatment-planning software that would enable the preparation of patient-specific treatment plans. To this end, we have developed a Web-based treatment-planning software for planning electroporation-based treatments that does not require prior engineering knowledge from the user (e.g., the clinician). The software includes algorithms for automatic tissue segmentation and, after segmentation, generation of a 3D model of the tissue. The procedure allows the user to define how the electrodes will be inserted. Finally, electric field distribution is computed, the position of electrodes and the voltage to be applied are optimized using the 3D model and a downloadable treatment plan is made available to the user.     

Epilepsy Associated Depression: An Update on Current Scenario,Suggested Mechanisms,and Opportunities

Depression is one of the most frequent psychiatric comorbidities associated with epilepsy having a major impact on the patient’s quality of life. Several screening tools are available to identify and follow up psychiatric disorders in epilepsy. Out of various psychiatric disorders, people with epilepsy (PWE) are at greater risk of developing depression. This bidirectional relationship further hinders pharmacotherapy of comorbid depression in PWE as some antiepileptic drugs (AEDs) worsen associated depression and coadministration of existing antidepressants (ADs) to alleviate comorbid depression has been reported to worsen seizures. Selective serotonin reuptake inhibitors (SSRIs) and selective serotonin and norepinephrine reuptake inhibitors (SNRIs) are first choice of ADs and are considered safe in PWE, but there are no high-quality evidences. Similar to observations in people with depression, PWE also showed pharmacoresistant to available SSRI/SNRIs, which further complicates the disease prognosis. Randomized double-blind placebo-controlled clinical trials are necessary to report efficacy and safety of available ADs in PWE. We should also move beyond ADs, and therefore, we reviewed common pathological mechanisms such as neuroinflammation, dysregulated hypothalamus pituitary adrenal (HPA) axis, altered neurogenesis, and altered tryptophan metabolism responsible for coexistent relationship of epilepsy and depression. Based on these common pertinent pathways involved in the genesis of epilepsy and depression, we suggested novel targets and therapeutic approaches for safe management of comorbid depression in epilepsy.

     

Drug Addiction,Psychotic Illness and Brain Self-Stimulation: Effective Treatment and Explanatory Hypothesis

Similarities between drug addiction and psychotic illness suggested that drug addicts could be treated with intensive ECT and phenothiazine drugs, a therapeutic approach effective in more serious psychotic illnesses.The use of this intensive treatment method is described in six drug addicts. Successful results were achieved in four patients who have been followed up for two to five years. The treatment program, the preliminary investigations and the follow-up procedures are described.Particular reference is made to the brain self-stimulation studies of Olds and others in animals, and those of Heath in man. A hypothesis is advanced to explain the various aspects of the clinical picture in both psychotic illness and drug addiction.The intensive method of treatment should be considered for drug addicts whose prognosis is otherwise poor. Further investigations along the lines of the proposed hypothesis might be profitable in other types of abnormal and maladaptive behaviour.     

The Effect of ELF Magnetic Field on Tumor Growth after Electrochemotherapy

From a fundamental point of view, chemotherapy is the most widely used treatment for cancers despite its side effects on normal cells and tissues. Electrochemotherapy (ECT) is a method for increasing the permeability of cancer cells to drugs and, hence, decreasing their dosage. It apparently creates electropores on the cell membrane using electric pulses. ECT can decrease tumor volume; but this effect is not permanent, and partial regrowth has been reported. The aim of this study was to investigate the potential of magnetic fields in preventing the regrowth of tumors after ECT. Tumoral Balb/c mice were exposed to a magnetic field (15 mT, 50 Hz) for 12 days after treating additionally with 70 V/cm electric pulses and bleomycin at the first day. The magnetic field caused a significant reduction in tumor volumes, while there was no significant difference between the ECT and the electroporation with ECT and magnetic field groups. The exploited magnetic field (15 mT, 50 Hz) could decrease the tumor growth rate significantly, without any effect on ECT efficiency.     

Unipolar late-onset depression: A comprehensive review

BACKGROUND: The older population increases all over the world and so also does the number of older psychiatric patients, which manifest certain specific and unique characteristics. The aim of this article is to provide a comprehensive review of the international literature on unipolar depression with onset at old age. METHODS: The authors reviewed several pages and books relevent to the subject but did not search the entire literature because of it's overwhelming size. They chose to review those considered most significant. RESULTS: The prevalence of major depression is estimated to be 2% in the general population over 65 years of age. The clinical picture of geriatric depression differs in many aspects from depression in younger patients. It is not yet clear whether it also varies across cultures and different socio-economic backgrounds. Biological data suggest that it is associated with an increased severity of subcortical vascular disease and greater impairment of cognitive performance. Many authors consider the existence of a somatic disorder to be related to the presence of depression in late life, even constituting a negative prognostic factor for the outcome of depression. Most studies support the opinion that geriatric depression carries a poorer prognosis than depression in younger patients. The therapeutic intervention includes pharmacotherapy, mainly with antidepressants, which is of established value and psychotherapy which is not equally validated. CONCLUSION: A significant number of questions regarding the assessment and treatment of geriatric depression remain unanswered, empirical data are limited, and further research is necessary.