Showing papers on "Treatment-resistant depression published in 2005"

A patient with a resistant major depression disorder treated with deep brain stimulation in the inferior thalamic peduncle.

Abstract: Objective and importance The present report explored the effect of electrical stimulation on the inferior thalamic peduncle in a patient with resistant major depression disorder (MDD). Clinical presentation This report refers to a 49-year-old woman with a history of recurrent episodes of major depression for 20 years (12 episodes and 2 hospitalizations), fulfilling Diagnostic and Statistical Manual of Mental Disorders, 4th edition, revised, criteria for MDD; in addition, the patient met criteria for borderline personality disorder and bulimia. Her longest episode of depression with suicidal ideation began 5 years before surgery. The patient's symptom array responded poorly to different combinations of antidepressants, cognitive therapy, and electroconvulsive therapy, which induced improvement only for short periods of time. Immediately before surgery, her Global Assessment of Functioning score was 20 and her Hamilton Depression Scale score ranged from 33 to 42. The patient was proposed for surgery for MDD. Intervention The patient had bilateral eight-contact electrodes stereotactically implanted for stimulation of areas at and around the inferior thalamic peduncle. Electrode position was corroborated by unilateral electrical stimulation searching for recruiting responses and regional direct current shifts in the electroencephalogram. Recording electrodes were replaced by tetrapolar electrodes for deep brain stimulation and connected to an internalized stimulation system for continuous bipolar stimulation at 130 Hz, 0.45 milliseconds, 2.5 V. Bimonthly follow-up included psychiatric and neuropsychological evaluations performed over the course of 24 months. After 8 months of ON stimulation, the patient entered a double-blind protocol with stimulators turned OFF. Improvement of depression measured by the Hamilton Depression Scale score was evident after initial placement of electrodes without electrical stimulation. Depression relapsed partially at the end of the first week. Electrical stimulation further improved depression, normalizing depression scores and neuropsychological performance. Patient depression scores ranked between 2 and 8 during 8 months of ON stimulation without antidepressant medication. After stimulation was turned OFF, spontaneous fluctuations in patient symptoms reflected by Hamilton Depression Scale and Global Assessment of Functioning scores were documented; these fluctuations disappeared after stimulation was turned on by Month 20. Conclusion Complicated patients with comorbid conditions are common referrals to psychosurgery services. In this report, we present promising results of electrical stimulation of the inferior thalamic peduncle to treat recurrent unipolar depression in a patient with MDD and borderline personality disorder who responded poorly to treatment.

Olanzapine/fluoxetine combination for treatment-resistant depression: a controlled study of SSRI and nortriptyline resistance.

Abstract: BACKGROUND This 8-week, double-blind, multicenter study was undertaken to replicate, in a larger sample of patients with treatment-resistant major depressive disorder (MDD; DSM-IV criteria), the results of a pilot study of the olanzapine/fluoxetine combination. METHOD The study was begun in August 1999. The primary entry criterion was a history of failure to respond to a selective serotonin reuptake inhibitor (SSRI). Patients (N = 500) who subsequently failed to respond to nortriptyline during an open-label lead-in phase were randomly assigned to 1 of 4 treatment groups: olanzapine (6-12 mg/day) plus fluoxetine (25-50 mg/day) combination, olanzapine (6-12 mg/day), fluoxetine (25-50 mg/day), or nortriptyline (25-175 mg/day). The primary outcome measure was baseline-to-endpoint mean change in score on the Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS At the 8-week study endpoint, MADRS total scores decreased by a mean 8.7 points from baseline (28.5) with the olanzapine/fluoxetine combination, 7.0 points from baseline (28.4) with olanzapine (p = .08), 8.5 points from baseline (28.4) with fluoxetine (p = .84), and 7.5 points from baseline (28.8) with nortriptyline (p = .30), with no significant differences among the therapies. The olanzapine/fluoxetine combination was associated with significantly (p < or = .05) greater improvement (decrease) in MADRS scores than olanzapine at weeks 2, 4, 6, and 7; than fluoxetine at weeks 2 through 5; and than nortriptyline at weeks 1 through 4. A post hoc analysis of a subgroup of patients who had an SSRI treatment failure during their current MDD episode (N = 314) revealed that the olanzapine/fluoxetine combination group had a significantly (p = .005) greater decrease in MADRS scores than the olanzapine group at endpoint. Safety data for the olanzapine/fluoxetine combination were similar to those for its component monotherapies. CONCLUSIONS The olanzapine/fluoxetine combination did not differ significantly from the other therapies at endpoint, although it demonstrated a more rapid response that was sustained until the end of treatment. The results raised several methodological questions, and recommendations are made regarding the criteria for study entry and randomization.

Low frequency rTMS stimulation of the right frontal cortex is as effective as high frequency rTMS stimulation of the left frontal cortex for antidepressant-free, treatment-resistant depressed patients.

Abstract: Background. Repetitive transcranial magnetic stimulation (rTMS) is a promising relatively non-invasive alternative for the treatment of depression. The purpose of this study was to compare the apparent effectiveness of high frequency (20 Hertz) rTMS applied over the left dorsolateral prefrontal cortex (DLPFC) with that of low frequency (1 Hz) rTMS applied over the right DLPFC.Methods. Twenty-eight antidepressant-free adults with major depressive (n = 25) or bipolar (n = 3) disorder (not on mood stabilizers) in a current major depression (Hamilton Rating Scale for Depression [HAM-D-21] ≥ 18; Mean = 24.5, SD = 5.51) were treated (14 right, 14 left) for 4 weeks.Results. Overall paired t-tests revealed a significant reduction in mean HAM-D-21, Beck Depression Inventory (BDI-II), and Clinical Global Impression of Change (CGIC) scores at the end of treatment for both groups (high frequency left DLPFC and low frequency right DLPFC). The treatment response rate found (32%) was typical of other response rates repo...

Empirical testing of two models for staging antidepressant treatment resistance.

Abstract: Background:An increasing amount of attention has been paid to treatment resistant depression. Although it is quite common to observe nonremission to not just one but consecutive antidepressant treatments during a major depressive episode, a relationship between the likelihood of achieving remission

Issues in treatment-resistant depression.

Abstract: Major depressive disorder is a debilitating disease that imposes significant social and economic burdens not only on patients but also on society. Although various treatment options are available, treatment-resistant depression is common. Determining the exact prevalence of treatment-resistant depression is difficult because definitions vary, as do definitions of antidepressant response. Operational definitions of antidepressant response, nonresponse, partial response, and remission will be discussed in this article. Pharmacotherapy options for patients with treatment-resistant depression include augmentation, combination, and switching therapies; however, data from controlled clinical trials supporting these therapies are limited. Electroconvulsive therapy and psychotherapy offer additional treatment strategies. New nonpharmacologic therapies are under investigation. Remission is the goal of treatment.

Method and system to provide therapy for depression using electroconvulsive therapy(ECT) and pulsed electrical stimulation to vagus nerve(s)

Abstract: A method and system for providing therapy or alleviating the symptoms of depression (including bipolar depression, unipolar depression, severe depression, treatment resistant depression, and melancholia), by providing electroconvulsive therapy (ECT) to the brain and pulsed electrical stimulation to the vagus nerve(s) for afferent neuromodulation. ECT is provided via two electrodes placed on the head, either in the unilateral or bilateral configuration. Constant-current (or constant-voltage) stimuli are provided using brief-pulsed outputs at frequencies between 30 Hz and 100 Hz. The transcranial stimuli delivered are strong enough to induce seizures. Pulsed electrical stimulation to the vagus nerve(s) may be provided continuously in ON-OFF repeating cycles. The two electrical stimulation therapies (ECT and VNS) may be given in any order, any combination, or any sequence as determined by the physician. The two electrical stimulation therapies may also be used with or without pharmaceutical therapy. Pulsed electrical vagus nerve stimulation (VNS) may be provided using an implanted pulse generator (IPG) or an external stimulator used in conjunction with an implanted stimulus-receiver. In one aspect of the invention the pulse generator system may comprise communication capabilities for networking over a wide area network, for remote interrogation and programming.

Treatment-resistant depression: resistant to definition?

Abstract: Objective: To better define treatment-resistant depression (TRD) so as to assist clinical management and refine treatment guidelines. Method: In this study, we examine a broad range of clinical variables in depressed patients (n = 196) referred to a tertiary referral Mood Disorders Unit (MDU). Information was collected from patients, referrers and assessors over a period of 32 months and included evaluations of treatments, treatment resistance and related variables. Data were analysed across trichotomized ‘high’, ‘low’ and ‘no’ treatment resistance groupings of patients. Results: A significantly greater proportion of patients with melancholia were amongst the high TRD group, and this was consistent across different strategies for evaluating melancholia. Conclusion: Melancholia perhaps provides a prototypic TRD subset that perhaps reflects some innate aspects of melancholic depression or factors such as the impact of ageing. Research into TRD is needed to both replicate this finding and perhaps explicate it further.

Ropinirole in treatment-resistant depression: a 16-week pilot study.

Abstract: Objective: The study aimed to assess the antidepressant efficacy and tolerability of adjunctive ropinirole in outpatients with treatment-resistant depression (TRD). Method: The study sample consisted of patients with a major depressive episode (diagnosed according to DSM-IV criteria) and TRD. Ropinirole 0.25 to 1.5 mg daily was added to tricyclic antidepressants or selective serotonin reuptake inhibitors. We conducted assessments at baseline and at weeks 2, 4, 8, 12, and 16. We defined response as a 50% or greater reduction of the Montgomery–Asberg Depression Rating Scale (MADRS) total score plus a score of 1 (“very much improved”) or 2 (“much improved”) on the Clinical Global Impression of Improvement scale at endpoint. Tolerability was monitored with the Dosage Record Treatment Emergent Symptom Scale. Results: Seven patients had major depressive disorder, and 3 had bipolar II disorder. The mean maximum dose of ropinirole was 1.33 mg daily. Mean (SD) scores on the MADRS decreased from 29.6 (7.6) at baseline to 16.9 (12.1) at endpoint (P < 0.02). At endpoint, 4 of 10 (40%) patients were responders. Two patients discontinued ropinirole because of dizziness. Conclusions: These pilot data suggest that, in selected cases of TRD, ropinirole augmentation of antidepressants is effective and relatively well tolerated. (Can J Psychiatry 2005;50:357–360) Information on author affiliations appears at the end of the article.

The effectiveness of psychological treatments for treatment-resistant depression: a systematic review.

Abstract: Objective: A systematic review of all studies (controlled and uncontrolled) to evaluate psychological interventions with treatment-resistant depression. Method: A systematic search to identify studies evaluating a psychological intervention with adults with a diagnosis of major depressive disorder who had not responded to at least one course of antidepressant medication. Results: Twelve studies met inclusion criteria, of which four were controlled and eight uncontrolled. Treatment effect sizes were computable for four studies and ranged from 1.23 to 3.10 with a number of better quality studies demonstrating some improvements in patients following a psychological intervention. Conclusion: Psychological treatments for depression are commonly delivered and often recommended following the failure of medication. The paucity of evidence for their effectiveness in these situations is a significant problem. There is a need for studies with a strong controlled design investigating the effectiveness of psychological treatments for patients with treatment-resistant depression.

Lamotrigine augmentation strategy for patients with treatment-resistant depression.

Abstract: Objective:To investigate if lamotrigine added to an antidepressant regimen reduces the symptoms of major depression in treatment-resistant patients.Introduction:Charts were retrospectively reviewed for 34 patients (36–63 years of age) with major depressive disorder who received lamotrigine augmentation to the antidepressant regimen for treatment-resistant depression (TRD). Data collection occurred at baseline and at an average of 30 (Time 2), 78 (Time 3), 167 (Time 6), and 356 days (Time 12), thereafter, using a “Medication Visit by MD” scale for collection of target symptom data at each timepoint.Results:Following the addition of lamotrigine to the antidepressant regimen (mean dose of 43, 63, and 113 mg/day for Time 3, Time 6, and Time 12, respectively), a statistically significant reduction of scores was shown as early as Time 2 for target symptoms of depressed mood, loss of interest, anxiety, irritability, (low) energy, and cognitive impairment. The difference from baseline remained statistically significant at Time 3, Time 6, and Time 12 (with the exception of irritability, which was not statistically significant at Time 6). “Patient's response” also reflected statistically significant improvement at each time period compared with baseline. The most common side effect reported and reason for discontinuation was tiredness.Discussion:Because TRD is a clinical condition that can present with severe and disabling symptoms, many clinicians are faced with an urgent need to find relief for their patients. Trying to achieve symptom improvement in a timely manner during a medication change can be challenging and difficult. This can be managed by an augmentation strategy using a psychotropic add-on to an existing medication regimen. Our results show the benefits of lamotrigine augmentation to an antidepressant regimen. Prospective, controlled clinical trials with larger sample size are needed to confirm our results.Conclusion:In this retrospective chart review, augmentation with lamotrigine was a tolerable and efficacious strategy for treating patients with TRD.

Potentiation strategies for treatment‐resistant depression

Abstract: Objective: To review the pharmacological basis of antidepressant potentiation in combination therapy and the clinical evidence for its efficacy. Method: Literature searches were undertaken and the results reviewed. Results: Treatment-resistant depression is common (15–30%). Various strategies exist for dealing with resistant depression, including pharmacological potentiation, i.e. adding a treatment that itself does not have antidepressant actions but that enhances the efficacy of the original treatment. Lithium, triiodothyronine (T3) and buspirone are the best studied potentiating drugs, although other options include pindolol, dopaminergic agents, second-generation antipsychotics, psychostimulants, hormones and anticonvulsants. Conclusion: Several pharmacological potentiation strategies exist. Whilst good evidence exists for lithium combined with antidepressants, although good results have also been reported with augmentation strategies involving T3 or buspirone.

New drugs, old problems: Revisiting... Pharmacological management of treatment-resistant depression

Abstract: Effective pharmacological management of depression resistant to antidepressant medication is best carried out in the context of a supportive and collaborative relationship, following a mutually agreed care plan. Simpler pharmacological approaches such as switching antidepressant classes are tried first, then augmentation is used if needed. New classes of antidepressants have made antidepressant combination a popular augmentation strategy, but lithium addition has most supporting evidence. The use of atypical antipsychotics as augmenting agents is increasing. For patients unresponsive to these strategies, monoamine oxidase inhibitors and electroconvulsive therapy remain important. Large randomised pragmatic trials are needed to help clinicians and patients make better treatment choices.

Multimodal therapy of treatment resistant depression : A study and analysis

Abstract: Objective:To demonstrate through the use of a case study, the application of cognitive psychotherapy in the treatment of resistant depression.Method:The case of a woman with an 18-month history of resistant depression associated with low self-esteem, guilt and shame, who failed to respond to three therapeutic trials of antidepressants is described. A detailed description of a CBT intervention over 12 sessions is given.Result:Clear improvements on assessments of mood and hopelessness, along with overall improvements in social and occupational functioning were noted.Conclusion:These improvements were attributed to a combination of CBT and pharmacotherapy, where pharmacotherapy alone failed to alleviate symptoms. A concise literature review revealed relatively few published trials of psychological treatments, and a lack of clear guidelines on pharmacological treatments. More research is needed to explore the efficacy of psychological therapies for treatment resistant depression.

Method of diagnosing, treating and educating individuals with and/or about depression

Abstract: The present invention relates to methods of correcting misconceptions in the DSM, which can affect improved diagnosis and testing for depression, resulting in better patient satisfaction and global improvement. Also provided are methods comprising administering various medications to produce a “pseudo-placebo” effect in depression, which can guide in selecting a particular treatment method for a more effective antidepressant effect. Another aspect of the invention relates to clinical neuroplasticity in depression by providing a method that increases patient compliance with medication, decreases the bias or prejudice in the public against depression/mental illness, decreases the percentage of treatment resistant depression, decreases patients' resistance and inappropriate use of less effective treatment or treatment without medication because of the existing misperception. Similar methods also can be used successfully for other conditions where depressive symptoms are often present as coexisting condition, such as nicotine addiction, smoking cessation, overweight/weight control and pain management.

Treatment Options in Treatment-Resistant Depression

Abstract: Treatment-resistant depression, or difficult-to-treat depression is emerging as a focus of scientific endeavor. Serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors are no longer "new" antidepressants, and most recent phase II and phase III studies attempting to identify agents with novel mechanisms of action have been unsuccessful. Unfortunately, 30% to 60% of patients treated with the currently approved antidepressant medications do not receive adequate relief of symptoms of major depressive disorder from the initial treatment intervention. In fact, only approximately 35% of patients in rigorously-controlled clinical research studies (those having a score of <8 on the Hamilton Rating Scale for Depression) benefit enough from initial treatment to be classified as fully remitted. Good clinicians are frequently challenged to devise alternatives for these difficult-to-treat patients. This article reviews the current treatment augmentation options and the rationale for their use.

Electroconvulsive therapy in treatment-resistant depression

Abstract: What is the role of electroconvulsive therapy (ECT) in the treatment of mood disorders, especially treatment-resistant depression (TRD)? While many have thought that ECT has been replaced by pharmacotherapy, ECT is still frequently used, with the number of treatments conducted annually in the United States exceeding coronary bypass, appendectomy, tonsillectomy, and hernia repair. Controlled studies and clinical experience indicate that the short-term efficacy of ECT in major depression is comparable, and likely superior, to that of any other antidepressant treatment. Patients with TRD consume a disproportionate share of medical resources and this condition often presents extraordinary burdens to the individual, family, and society. Relative to any other antidepressant treatments, ECT has the highest rate of response/remission, the fastest onset of symptom relief, and the most complete symptom relief. However, ECT has two major drawbacks that limit its use: its effects on memory and high rate of relapse. Current research is directed at improving cognitive outcomes and identifying more effective prophylactic treatment following ECT. Novel innovations include methods to produce seizures with focal onset and limited propagation. Such modifications have the potential to markedly reduce the adverse effects of ECT without compromising efficacy.

The combined treatment of venlafaxine and ECT in treatment-resistant depressive patients.

Abstract: Objective To evaluate the efficacy and safety of the combination treatment of ECT and venlafaxine among treatment-resistant depressive patients. Methods We reviewed 21 depressive patients who were treated with a combination of electroconvulsive therapy (ECT) and venlafaxine. The indication of the ECT-venlafaxine treatment was inadequate response to at least one antidepressant trial of adequate doses and duration. Propofol was used as an anesthetic agent during ECT treatments. Results Ninety percent of the patients benefited from the combined treatment. The responsivity to the combination treatment was not associated with high dose of venlafaxine. In most of the patients, the combined treatment was safe and well tolerated. Adverse reactions occurred in 57% of the patients and included concentration difficulties (four patients), memory problems (seven patients) and headache (one patient). No asystole was observed. Treatment was safe with a low dose of venlafaxine equal to or lower than 225 mg/day. Conclusions It seems that treatment of ECT combined with low dose venlafaxine and propofol as anesthetic agent is effective and safe. This strategy may be a therapeutic option in treatment-resistant depressive patients.

Olanzapine plus venlafaxine in treatment-resistant depression.

Abstract: Depression, one of the commonest illnesses, is often under-diagnosed and under-treated (Cowen, 1996; Chehil et al., 2000). Furthermore, of those who are treated adequately, only about 70% show a response to treatment and only about 40% reach full remission (Cowen, 1996; Chehil et al., 2000). The consequences of failure to achieve and sustain full remission are numerous and include further relapse, recurrence, chronicity, risk of suicide and occupational and personal difficulties (Cowen, 1996; Chehil et al., 2000). Factors that cause lack of response include comorbidity of other illnesses, lack of compliance and effectiveness of medication, dose and duration. Lack of response to adequate trials of two antidepressants of different classes is defined as treatment-resistant depression (TRD). Adequate trial is defined as adequate dose and duration. Up to 30% of patients fall into the category of TRD (Cowen, 1996; Chehil et al., 2000; Dursun and Devarajan, 2001; Dursun et al., 2001). Management of TRD includes review of diagnosis, optimization of medications, establishment of compliance, combination, augmentation, switching strategies and other non-pharmacological treatments. However, there are no established guidelines that govern switching, augmenting or combining strategies. Furthermore, to our knowledge, no one strategy has been shown to be superior to another strategy. We present a naturalistic and case series of neuroscience-based pharmacological strategy (Zhang et al., 2000) to manage TRD. Our patients include four males and four females (eight consecutive patients suitable for the combination treatment) between 42 and 68 years of age. The dose range of the medication was 300mg to 450mg for Venlafaxine and between 5mg and 20mg for Olanzapine. Patients received both medications simultaneously and doses titrated gradually according to clinic response and tolerability. The pre-treatment HAM-D scores were 38, 36, 26, 34, 33, 33, 38 and 28. Post-treatment scores following 10 weeks of treatment were 8, 7, 9, 6, 8, 5, 7 and 9. CGI scores also confirmed the above outcome. The adverse effects, which included headache, nausea, insomnia and dry mouth, were mild and tolerable. Patients A, C, D, F and H gained less than 1kg in weight. In the other three patients, the weight gain ranged between 1.5kg and 4kg. No patients experienced any extra pyramidal symptom, and no other serious side-effects, including hypertension, were observed. Atypical antidepressants in combination with SSRI have been shown to be effective in TRD. Our naturalistic case series outcome appear to be in agreement with the published randomized controlled trials indicating that Olanzapine in combination with Fluoxetine is an effective and safe treatment strategy for TRD (Shelton et al., 2001; Matthews et al., 2002). However, the underlying mechanism(s) of action are less clear. The underlying mechanism may not be due to a pharmacokinetic interaction as Olanzapine is known to be metabolized by multiple metabolic pathways mediated by CYP450–1A2 and CYP450–2D6 and Venlafaxine is not known to cause any significant enzyme induction or inhibition. However, the effectiveness of this combination may be due to a pharmacodynamic interaction targeting multiple neurotransmitters. In fact, Olanzapine, in combination with Fluoxetine, has been shown to be more robust than other atypicals in increasing the neuroamines in the prefrontal cortex of rats (Zhang et al., 2000). These monoamines may cause symptom reduction by improving the inhibitory modulation of the frontal cortex over the limbic system, possibly the amygdaloid complex (Morris et al., 1999). Furthermore, atypical antipsychotics are shown to normalize sleep architecture as well (Sharpley et al., 2000, 2001). Lack of substantial weight gain is an additional benefit and may be attributed to the thermogenic properties of norepinephrine and dopamine enhanced by Venlafaxine.

Focal brain stimulation for treatment-resistant depression: Transcranial magnetic stimulation, vagus-nerve stimulation, and deep-brain stimulation

Abstract: There is an increased interest in focal brain stimulation as a potential treatment for depression. This is largely due to an attempt to find treatments for depression that have efficacy similar to electroconvulsive therapy (ECT) but are not associated with the same limitations as ECT. This article describes three techniques for focal brain stimulation: transcranial magnetic stimulation, vagus-nerve stimulation, and deep-brain stimulation. It also discusses the data supporting their use in treatment-resistant depression.