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02.07.2015

Effective treatment for unipolar depression, tinnitus treatment youtube - Reviews

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Comparative efficacy of cognitive therapy and pharmacotherapy in the treatment of depressed outpatients. Medications versus cognitive behavior therapy for severely depressed outpatients: meta-analysis of four randomized comparisons.
Treatment of major depression with psychotherapy or psychotherapy-pharmacotherapy combinations. Six-year outcome for cognitive behavioral treatment of residual symptoms in major depression.
Systematic review of efficacy of cognitive behaviour therapies in childhood and adolescent depressive disorder. Effective personalized treatment recognizes bipolar disorder as a biopsychosocial disorder, but mood-stabilizing medications are the backbone of treatment. An increasingly intriguing aspect of treatment with lithium and atypical antipsychotics involves their effect on BDNF. A meta-analysis comprising 16,000 patients who had acute mania found that the most effective agents were haloperidol, risperidone, and olanzapine.
Psychotherapy is an integral part of the effective treatment of bipolar disorder, not just an augmentation strategy. Some authors suggest that there has been no truly revolutionary drug for the treatment of mood disorders for numerous decades. Two large randomized placebo-controlled trials8,9 demonstrated aripiprazole’s efficacy as augmentation treatment in unipolar depression. With the relative dearth of novel agents for mood disorders, it is worth surveying drugs that are in development. Agomelatine, a melatonergic agonist at melatonin (MT)1 and MT2 receptors and a 5-HT2C antagonist, is in phase III clinical trials in the United States for the treatment of MDD. The monoaminergic hypothesis of depression underlies existing antidepressants and the preceding compounds. Numerous triple reuptake inhibitors have shown promise in animal models of depression and have progressed to clinical trials. Numerous strategies have been employed to regulate the HPA axis in the treatment of depression. Mifepristone is a glucocorticoid receptor-2 antagonist and progesterone receptor, which is approved by the FDA for termination of early pregnancy. Numerous CRF-1 receptor antagonists have been developed for depression and anxiety disorders. Saredutant is a NK-2 receptor antagonist that had progressed to the point that an application for approval for depression seemed to be forthcoming. The N-methyl-D-aspartate excitotoxic amino acid (NMDA) receptor is a subtype of glutamate receptor and has been the subject of investigation regarding depression. Several studies9-11 have shown that cognitive therapy is superior to no treatment or to placebo.
A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. Recognizing that the primary mood state may be irritability rather than euphoria increases the likelihood of diagnosis as does the recognition that symptoms often last fewer than the 4 days required for diagnosis by DSM-IV.2 Focusing more on overactivity than mood change further improves diagnostic accuracy, and the use of structured questionnaires is helpful. No matter how effective a medication is, it will not relieve symptoms if it is not being taken. His Web site, PsychEducation.org, gathers no information on visitors and produces no income for him or others. In the last 2 years, only one new drug has been approved for the treatment of major depressive disorder, desvenlafaxine; during this time, the other medications approved for the treatment of depression or bipolar disorder have been atypical antipsychotics that have already been approved for the treatment of schizophrenia. The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study1 reported a cumulative 67% remission rate after four treatment steps.
Recent Food and Drug Administration approvals for bipolar disorder and unipolar depression have been for compounds that have already been approved for other disorders or reformulations or metabolites of already available medications.
Quetiapine has received approval for maintenance treatment of bipolar disorder as an adjunct to lithium or divalproex.
Paliperidone, the active metabolite of risperidone and recently approved for schizophrenia, is in phase III trials for the treatment of manic and mixed episodes. DOV 21,947 has completed eight Phase I trials and is now recruiting for Phase II clinical trials for the treatment of MDD. Steroid synthesis inhibitors such as ketoconazole, metyrapone, or aminogluthemide have been studied with mixed results.30 In particular, two approaches are being actively pursued as treatments for mood disorders, namely, glucocorticoid receptor antagonists and CRF-1 receptor antagonists. There have been multiple published studies examining it’s efficacy in depression with psychosis.
In an open-label study of 20 patients, patients who received R121919 40–80 mg had significant decreases in HAM-D and Beck Depression inventory scores over 30 days.
A double-blind placebo-controlled study39 of >162 patients demonstrated superiority to placebo in patients with depression with melancholic features, although a dose-finding trial40 has failed to show separation from placebo.
It has multiple mechanisms of action which include inhibition of glutamate release through sodium channels, similar to that of lamotrigine, and the enhancement of glutamate reuptake.43 Two open-label studies44,45 have been performed in unipolar depression, and one open-label study46 in bipolar depression.


However, the need for intravenous infusion and ketamine’s notoriety as a potential drug of abuse may limit its ultimate utility as an antidepressant. Predictors of recurrence in bipolar disorder: primary outcomes from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Aripiprazole monotherapy in nonpsychotic bipolar I depression: results of 2 randomized, placebo-controlled studies. The efficacy and safety of aripiprazole as adjunctive therapy in major depressive disorder: a multicenter, randomized, double-blind, placebo-controlled study. The efficacy and safety of aripiprazole as adjunctive therapy in major depressive disorder: a second multicenter, randomized, double-blind, placebo-controlled study.
A double-blind, placebo-controlled study of the efficacy and safety of desvenlafaxine succinate in the treatment of major depressive disorder J Clin Psychiatry. A randomized, double-blind, placebo-controlled trial of desvenlafaxine succinate in the treatment of major depressive disorder.
Determination of the dose of agomelatine, a melatoninergic agonist and selective 5-HT(2C) antagonist, in the treatment of major depressive disorder: a placebo-controlled dose range study. Severe depression and antidepressants: focus on a pooled analysis of placebo-controlled studies on agomelatine. Vilazodone: evidence for efficacy and tolerability in the treatment of major depressive disorder. Mifepristone versus placebo in the treatment of psychosis in patients with psychotic major depression.
Substance P receptor antagonists in psychiatry: rationale for development and therapeutic potential. Distinct mechanism for antidepressant activity by blockade of central substance P receptors.
Lack of efficacy of the substance p (neurokinin1 receptor) antagonist aprepitant in the treatment of major depressive disorder. Demonstration of the efficacy and safety of a novel substance P (NK1) receptor antagonist in major depression.
Preliminary evidence of riluzole efficacy in antidepressant-treated patients with residual depressive symptoms. An open-label trial of the glutamate-modulating agent riluzole in combination with lithium for the treatment of bipolar depression. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. A double-blind, placebo-controlled study of memantine in the treatment of major depression.
Studies have shown that cognitive therapy is an effective treatment for depression and is comparable in effectiveness to antidepressants and interpersonal or psychodynamic therapy. Although it is unclear who benefits most from cognitive therapy, motivated patients who have an internal locus of control and the capacity for introspection likely would benefit most.During cognitive therapy, the therapist helps the patient work through several steps.
Two comprehensive meta-analyses11,13 showed that cognitive therapy is as effective as interpersonal or brief psychodynamic therapy in managing depression.
Moreover, bipolar patients often use highly lethal means for suicide.1 Contributing factors include early age at disease onset, the high number of depressive episodes, comorbid alcohol abuse, a history of antidepressant-induced mania, and traits of hostility and impulsivity.
The FDA has approved Seroquel, Seroquel XR, and Symbyax (the combination of olanzapine and fluoxetine), for the acute treatment of bipolar depression.
The key to effective personalized treatment of bipolar disorder is a good patient-physician connection in which the patient is part of the treatment decision-making process.
There are, however, numerous medications in development for the treatment of mood disorders. However, the pharmacologic treatment of mood disorders remains an area of intense and exciting research. Applications have been made to the FDA for the extended-release version quetiapine for treatment indications for manic and depressed episodes of bipolar disorder, and for unipolar depression.
Sleep electroencephalogram studies indicated reversal of sleep architecture changes associated with depression.
Development on these two compounds for mood disorders has been halted, although aprepitant has been approved for the adjunctive treatment of chemotherapy-induced emesis. A proposed mechanism for the mood stabilizing and antidepressant effects of lamotrigine is the inhibition of glutamate release through its effect on sodium channels. The first study44 used riluzole 100–200 mg as monotherapy for unipolar depression for 19 patients. Memantine is a low-affinty NMDA antagonist used for the treatment of Alzheimer’s disease. The combination of cognitive therapy and antidepressants has been shown to effectively manage severe or chronic depression.
CBT should be strongly considered as initial therapy for patients with severe or chronic depression or for adolescents. Of 157 patients who had at least a 50% decrease in the YMRS score at week 1, 84% responded and 64% had symptom remission at 3 weeks.4 Clinically, a medication change should be considered for patients who do not demonstrate substantial benefit by week 1.


Desvenlafaxine is not predominately metabolized by the cytochrome P450 (CYP) system and is eliminated primarily by phase II metabolism; as a result, it has lower potential for drug interactions, especially with the CYP 2D6 pathway. This has been borne out clinically by studies indicating the effectiveness of buspirone, a 5-HT1 partial agonist, in the augmentation of SSRI treatment, most notably in the STAR*D trial. Results of a double-blind Phase I study with DOV 216,303 showed significant decreases in HAM-D scores after 2 weeks of treatment. However, development was halted when drug-induced reversible increases in liver enzymes were detected in a safety study, although this was thought to be unrelated to its principal method of action.33 Despite this setback, the exploration of CRF-1 receptor antagonists for the treatment of depression and anxiety disorders remains extremely active. These drugs may not only improve the efficacy of treatment, but could potentially improve the speed and tolerability of pharmacotherapy. A meta-analysis12 of four studies, which included 169 patients with major depression, showed similar results for tricyclic antidepressants and CBT.
Perhaps the most notable FDA indication is the approval of aripiprazole as an augmentation agent for the treatment of unipolar depression.
Although three Phase III clinical trials for mifepristone have failed to demonstrate efficacy versus placebo for depression with psychosis, trials continue to examine higher doses of 1,200 mg. Good evidence has shown that cognitive therapy reduces relapse rates in patients with depression, and some evidence has shown that cognitive therapy is effective for adolescents with depression. An important part of CBT for depression is scheduling pleasurable activities, especially with others, that usually give positive reinforcement.
The evidence suggests that cognitive therapy is a valid alternative to antidepressants for patients with mild to moderate depression and possibly for patients with more severe depression. There is also some evidence that buspirone is effective in treating sexual dysfunction brought on by SSRIs, although it is somewhat equivocal. Chronic high levels of cortisol are thought to contribute to hippocampal volume loss and possibly neurocognitive symptoms of depression. Significant decreases in depression occurred within 110 minutes after infusion, which persisted for 1 week. Curiously, two large studies7 were unable to demonstrate aripiprazole’s effectiveness as monotherapy for bipolar depression. Instead of a placebo arm, there was an active comparator arm using citalopram 20 mg BID, which also showed significant decrease in HAM-D scores in the same time period.28 Another triple reuptake inhibitor, GSK 372475, is also in phase II trials for depression. Furthermore, successful treatment of depression leads to normalization of cortisol levels and regulation of the HPA axis.
In another study,45 riluzole 100 mg was used as an augmentation strategy in unipolar depression for patients who had a HAM-D24 score >21 despite being on a stable dose of medication for at least 6 weeks. Glucocorticoid receptor antagonists and corticotropin releasing factor-1 antagonists, which seek to modulate the hypothalamic-pituitary-adrenal axis, are being explored for efficacy in the treatment of unipolar depression. A third, SEP 225289, has started phase I clinical trials.15 Conceptually, triple reuptake inhibitors are quite appealing and are the natural extension of the monoaminergic hypothesis of depression, although questions remain about what the most effective balance of neurotransmitter action would be. Agents that modify the glutamatergic system, such as riluzole and ketamine, are being explored for treatment of bipolar and unipolar depression. Patients in both studies had significant drops in the Montgomery Åsberg Depression Rating Scale (MADRS) total score, the primary outcome measure. Forty percent of the 10 patients who completed the 6 weeks had responded and 30% were in remission.
Later evidence suggests that this combination may be more effective than either therapy alone for some patients.
This article reviews the rationale and evidence for these proposed agents in the treatment of mood disorders. Sexual dysfunction was examined using the Arizona Sexual Experiences Scale, and no significant differences were noted between treatment and placebo group.
Patients who responded seemed to respond rapidly in the first week and held durable responses for months. A meta-analysis17 that included six studies and 595 patients showed that patients with severe depression benefited from the combination of psychotherapy and pharmacotherapy. Furthermore, the investigators identified a genetic biomarker which identifies patients that had significantly more improvement after 8 weeks of vilazodone treatment.
Another open-label study46 looked at riluzole in addition to lithium for bipolar depression.
However, only two trials studied CBT, and patients with less severe depression gained little from the combination.17 A more recent study18 of 681 patients with chronic major depression compared nefazodone (Serzone), CBT, and combination therapy. Two small studies20,21 of 40 patients with unipolar major depression and residual symptoms following antidepressant therapy showed that patients treated with CBT initially had fewer residual symptoms and fewer depressive episodes after six years compared with those treated with clinical therapy.A more recent, larger study19 randomized 158 patients who did not respond to adequate antidepressant therapy to receive cognitive therapy with clinical management or clinical management alone. A meta-analysis22 of six studies with 191 patients showed that CBT was significantly more effective than placebo or inactive interventions in managing adolescent depressive disorder (36 versus 62 percent, NNT = 4).



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