Rapid Improvement Of Depressive Symptoms Research Articles

Total sleep deprivation followed by sleep phase advance and bright light therapy in drug-resistant mood disorders

Drug-resistant depression is a major therapeutic issue in psychiatry and the development of non-drug therapies that treat drug-resistant depression is required. Sleep deprivation (SD) is a non-drug treatment classified as a form of chronotherapy in addition to bright light therapy (BLT) and sleep phase advance (SPA). Combined chronotherapy is hypothesized to improve drug-resistant depression. In this study, we investigated the benefits of total sleep deprivation (TSD) followed by SPA and BLT in drug-resistant depression alongside ongoing antidepressant medication and observed the added effectiveness of the combined chronotherapy. Thirteen drug-resistant inpatients affected by a major depressive episode were studied. They were treated by TSD followed by SPA (three days) and BLT (five days) with ongoing drug treatment. Effectiveness was rated using the Hamilton Rating Scale for Depression (HAM-D), the Zung Self-Rating Depression Scale (SDS), and the Visual Analogue Scale (VAS) over 3 weeks. Significant improvements of depressive symptoms were observed in both objective mood ratings (HAM-D) and subjective mood ratings (SDS and VAS). Eight out of 13 patients maintained this responsiveness (50% or greater changes in HAM-D) across the study period. Moreover, no patients dropped out of the combined chronotherapy procedure. The study did not have a placebo group, and more subjects may be needed. The trial of combined chronotherapy successfully induced rapid improvement in depressive symptoms in drug-resistant patients without early relapse or obvious side effects.

Rapid improvement of depressive symptoms and cognition in an elderly patient with a single session of piano playing: a clinical treatment report

Music has been used as a non-pharmacological modality in the treatment of different conditions since ancient times. It has received attention in modern medicine in recent decades, particularly in geriatric population. The effects of music on mood and cognition are well documented. The aim of the current case report is to highlight the benefits of musical activities in the geriatric population. We report a naturalistic treatment outcome in an elderly patient on a geriatric psychiatric unit related to a single session of piano playing. A rapid and sustained improvement in mood and cognition of an elderly patient was observed after a single session of playing piano. Notwithstanding the limitations of a single subject, uncontrolled case study, the effect was dramatic. Our findings support previous claims regarding music therapy including effects of a single session music-based therapeutic interventions, and we conclude that music therapy for geriatric patients with mood and cognitive deficits is worth further systematic investigation.

Comorbid social anxiety disorder in clients with depressive disorders: Predicting changes in depressive symptoms, therapeutic relationships, and focus of attention in group treatment

The current study examined whether depressed outpatients with comorbid SAD respond differently to a cognitive-behavioral group intervention and if so, how and why. Using growth curve modeling, we found evidence that depressed clients with comorbid SAD had rapid improvement in depressive symptoms over the course of treatment and generally did not differ from those without comorbidity in developing close therapeutic relationships and modifying the direction of attentional focus away from the self. Non-linear effects demonstrated that rates of change in depressive symptoms, relationship variables, and focus of attention, were most rapid early in treatment. In contrast to hypotheses, trajectories of change in therapeutic relationships and attentional focus did not mediate the effect of SAD on treatment improvement in depressive symptoms. These findings suggest that comorbid SAD does not have a detrimental effect on the course of depression treatment and group-based treatments can be as beneficial for depressed individuals with comorbid SAD. It may be that group-based treatments for depression provide explicit opportunity for emotional processing in social situations (i.e., exposure) and hence mimic efficacious therapies for SAD.

The antidepressant effect of ketamine is not associated with changes in occipital amino acid neurotransmitter content as measured by [ 1H]-MRS

The NMDA receptor antagonist ketamine can induce a rapid improvement in depressive symptoms that often endures for days after a single intravenous dose. The pharmacodynamic basis for this effect is poorly understood. Using a proton magnetic resonance spectroscopy ([ 1H]-MRS) method that previously detected a normalization of amino acid neurotransmitter (AANt) content after chronic treatment with conventional antidepressant treatments, we examined whether the acute action of ketamine is associated with alterations in AANt content as well. Ten subjects with major depressive disorder (MDD) received saline, then ketamine in a fixed order, one week apart, under single-blind conditions. Each infusion was associated with three [ 1H] MRS scans (baseline, 3 h and 48 h post-infusion) that measured glutamate, GABA and glutamine within the occipital cortex. Rating scales were administered before, during and after each infusion. The rapid (1 h) and sustained (at least 7 days) antidepressant effect we observed after ketamine infusion was not associated with either baseline measures of, or changes in, occipital AANt content. Dissociative symptoms were not correlated with changes in depression scores. While our results indicate that changes in occipital AANt content are not a correlate of ketamine's antidepressant action, this may only apply to the regional and temporal windows of our MRS measurements.

Rapid improvement of depressive symptoms in suicide attempters following treatment with milnacipran and tricyclic antidepressants – a case series

Suicide is a serious social problem in many countries, including Japan. The majority of people who commit suicide suffer from depression. Suicide attempt patients suffering from serious physical injuries are initially treated in hospital emergency departments. The present post hoc analysis examined data from patients admitted to an emergency hospital for treatment of physical injuries, resulting from a suicide attempt, and initial psychiatric treatment for depression and prevention of future suicide attempts. The effects on depressive symptoms were studied in two groups of patients using the 17-item Hamilton depression scale (HAMD). One group (n = 6) had received intravenous tricyclic antidepressants (TCA) (amitriptyline or clomipramine) while the other group (n = 7) had been treated orally with milnacipran, a serotonin and norepinephrine reuptake inhibitor antidepressant. Prior to treatment the four highest scoring items on the HAMD scale were the same in both groups namely, item 1 (depressed mood), item 3 (suicidality), item 7 (interest in work and activities), and item 10 (psychic anxiety). After 1 week of treatment, mean global HAMD scores were significantly reduced in both groups. Treatment resulted in a significant reduction of five HAMD items in the TCA group, whereas in the milnacipran group 12 HAMD items were significantly reduced. Suicidality (item 3) was significantly improved by 1 week treatment with milnacipran, but not by TCAs. Milnacipran rapidly improved a wide range of depressive symptoms, including suicidality within the first week. The improvement with milnacipran would appear to be, at least, equivalent to that achieved with TCAs, possibly affecting a wider range of symptoms. Since milnacipran has been shown in comparative studies to be better tolerated than TCAs, this antidepressant offers an interesting option for the treatment of suicidal patients in an emergency setting.

Acute administration of ketamine reverses the inhibition of mitochondrial respiratory chain induced by chronic mild stress

Modulation and dysfunction of the glutamatergic system seems to be involved in depression. Recently a renewed interest in the glutamatergic system as a treatment option for major depression emerged by the finding that the glutamate N-methyl- d-aspartate (NMDA) antagonist ketamine leads to a rapid improvement of depressive symptoms. Several works support the hypothesis that metabolism impairment is involved in the pathophysiology of depression. We have also recently reported that mitochondrial respiratory chain complexes I, III and IV were inhibited in cerebral cortex and cerebellum of rats after 40 days of chronic mild stress (CMS), which is used as an animal model of depression. Thus, we investigated whether the inhibition of these enzymes may be reversed by acute administration of ketamine (15 mg/kg). We verified that CMS decreased the intake of sweet food and ketamine was not able to reverse such effect. Adrenal gland weight was increased in stressed rats and ketamine reversed this alteration. Control group gained weight after 40 days but stressed group did not gain weight after the same period. Stressed animals gained weight after acute administration of ketamine, when compared to the body weight assessed at the beginning of the experiment. Finally, we verified that complexes I, III and IV were inhibited after CMS in cerebral cortex and cerebellum and acute administration of ketamine reversed this inhibition. Based on the present findings, we hypothesized that CMS induces inhibition of mitochondrial respiratory chain (complexes I, III and IV) and that acute administration of ketamine reverses such effect.

Rapid Onset of Antidepressant Action

Current therapeutics of depression are similar in their time to antidepressant action and often take weeks to months to achieve response and remission, which commonly results in considerable morbidity and disruption in personal, professional, family, and social life, as well as risk for suicidal behavior. Thus, treatment strategies presenting a rapid improvement of depressive symptoms--within hours or even a few days--and whose effects are sustained would have an enormous impact on public health. This article reviews the published data related to different aspects of rapid improvement of depressive symptoms. Literature for this review was obtained through a search of the MEDLINE database (1966-2007) using the following keywords and phrases: rapid response, antidepressant, time to, glutamate, sleep, therapeutics, latency, and depression. The data obtained were organized according to the following topics: clinical relevance and time course of antidepressant action, interventions showing evidence of rapid response and its potential neurobiological basis, and new technologies for better understanding rapid anti-depressant actions. A limited number of prospective studies evaluating rapid antidepressant actions have been conducted. Currently, only a few interventions have been shown to produce antidepressant response in hours or a few days. The neurobiological basis of these rapid antidepressant actions is only now being deciphered. Certain experimental treatments can produce antidepressant response in a much shorter period of time than existing medications. Understanding the molecular basis of these experimental interventions is likely to lead to the development of improved therapeutics rather than simply furthering our knowledge of current standard antidepressants.

The glutamatergic system and its relation to the clinical effect of therapeutic-sleep deprivation in depression – An MR spectroscopy study

Rapid improvement of depressive symptoms occurs after the administration of the NMDA antagonist ketamine. Ketamine administration is accompanied by an increase in GLX (sum-peak of glutamate, glutamine (GLN) and GABA) and GLN in the brain, as measured by magnetic-resonance (MR) spectroscopy. In healthy subjects, we observed an increase in GLX and GLN levels after total sleep deprivation (TSD), which has a rapid antidepressant effects. We examined, if an increase in GLX or GLN is related to the therapeutic effect of TSD. We examined 13 patients with major depression by means of proton MR spectroscopy (field strength: 1.5 T) before and after 24 h of TSD. Two anatomical areas (dorsolateral prefrontal cortex (DLPC) and parieto-occipital cortex (POC)) were studied. In the DLPC TSD did not change GLX or its elements, whereas the total creatine and choline signal increased marginally. No change could be observed in the POC. For further exploration we took gender and the presence of vegetative characteristics of melancholic depression into account, i.e. the presence of early morning awakening, appetite and weight loss was taken into account, to define vegetative melancholia (VM). TSD led to an increase in GLX and GLN in the DLPC only of male patients. In patients with VM an increase in GLN occurred in this area. The low field strength limits the accuracy for GLX and GLN estimates. Despite the exploratory nature of the study, it nevertheless supports earlier data on the importance of glutamatergic neurotransmission and furthermore of gender and/or vegetative features in depression.

Adjunctive Aripiprazole for Bupropion-Resistant Major Depression

To examine the effects of adjunctive aripiprazole in patients with major depression refractory to adequate therapy with bupropion. Four consecutive patients diagnosed with major depression that was not responsive to a minimum of 2 months of therapy with bupropion 150-450 mg/day were given adjunctive aripiprazole 2.5-10 mg/day and followed for at least 4 months. Chart notes were used to record patient responses. All patients reported rapid improvement in depressive symptoms following the addition of low-dose aripiprazole. Antidepressant effects were sustained for at least 4 months in all patients; however, the mood disturbance subsequently returned in 2 patients. Adjunctive aripiprazole was well tolerated, with one patient developing akathisia that responded to lowering the aripiprazole dose and another exhibiting worsening of preexisting insomnia. Weight and metabolic parameters were not monitored during the observation period. Transitory improvements in depressive symptoms that occurred in some of the 4 patients may have been due to compensatory mechanisms in dopaminergic systems. Adjunctive use of the atypical antipsychotic aripiprazole has been demonstrated to benefit depressed patients who are resistant to selective serotonin-reuptake inhibitors. The response to aripiprazole in patients refractory to bupropion has not been previously reported. Adjunctive aripiprazole given in low doses resulted in rapid improvements in depressed patients who were refractory to adequate therapy with bupropion. Additional studies are required to determine whether these results can be generalized to other depressed individuals who are refractory to bupropion treatment.

Rapid early response, cognitive modification, and nonspecific factors in cognitive behavior therapy for depression: A reply to Tang and DeRubeis.

Tang and DeRubeis (this issue) challenge the Ilardi and Craighead (1994) hypothesis that nonspecific factors mediate a large proportion of clinical improvement In cognitive behavior therapy (CUT) for depression, and argue that Beck's cognitive hypothesis is not contradicted by the phenomenon of rapid early treatment response. They propose (a) that cognitive modification techniques are introduced in CBT as early as Session 2, (b) that dose-response analyses are inconsistent with the rapid early response pattern, and (c) that observed heterogeneity of patient temporal response curves is problematic for the nonspecific factors hypothesis. In response, we note that (a) there is no compelling evidence that cognitive modification techniques are routinely implemented prior to Week 3 of CBT, (b) disproportionately rapid improvement In depressive symptoms typically occurs over the first six sessions (3 weeks) of CBT, and (c) the two newly reported heterogeneous temporal response patterns are each consistent with the hypothesis of nonspecific mediation of clinical improvement.

Sequential administration of augmentation strategies in treatment-resistant obsessive-compulsive disorder: preliminary findings.

Given that an important proportion of patients with obsessive-compulsive disorder (OCD) fail to respond adequately to serotonin (5-HT) reuptake inhibitors (SRI), augmentation strategies aimed at enhancing further 5-HT transmission by different mechanisms were attempted sequentially in 13 SRI-resistant patients. Addition of the 5-HT1A l beta-adrenergic antagonist pindolol did not alter OCD symptomatology but produced a rapid improvement of depressive symptoms. The 5-HT1A agonist buspirone as well as 5-hydroxytryptophan, the immediate precursor of 5-HT, added to the SRI-pindolol regimen, were not effective in attenuating the intensity of OCD. Tryptophan, added to the SRI-pindolol regimen, produced a significant improvement after 4 weeks, with further amelioration after 6 weeks (36% decrease of the Yale-Brown Obsessive Compulsive Score), which was maintained with treatment prolongation.

Potential effect of enalapril on clomipramine metabolism

AbstractIn two patients treated for hypertension with enalapril for more than 12 months, clomipramine was introduced in small to moderate doses for the treatment of dysthymic disorders. Rapid improvement of depressive symptoms was noted, which was followed by signs of antidepressant overdosage. The blood levels of clomipramine and desmethylchlomipramine were high. After reducing the dose, the symptoms resolved and the blood level of antidepressant returned to the usual therapeutic range. Enalapril would appear to reduce the clearance of clomipramine; the association enalapril + clomipramine does not appear to modify blood pressure.

Treatment of Refractory Depression with Combination Reserpine and Tricyclic Antidepressant Therapy

Chronic reserpine use has been reported to precipitate severe depression in some individuals as a result of its amine-depleting action. However, early clinical studies demonstrated that acute administration of high doses of parenteral reserpine in combination with a tricyclic antidepressant could produce rapid improvement in depressive symptoms. Because these early studies defined treatment resistance as failure to respond to a brief course of treatment with a single tricyclic antidepressant, we performed a more stringent, placebo-controlled evaluation of high dose reserpine in nine depressives refractory to at least six previous drug treatments. Overall, neither reserpine nor placebo produced a meaningful decrease in depression ratings within 1 week of treatment; however, one patient did respond to a second course of reserpine. Side effects were mild to moderate in severity, and there were no cases of profound hypotension. Although the efficacy of this drug combination in severely refractory depressives was not confirmed, reserpine may still prove a useful adjunctive agent in some tricyclic-resistant depressed patients.