Adjunctive gabapentin in treatment-resistant depression: a retrospective chart review

BACKGROUND: Previous studies in predominantly bipolar patients have suggested that gabapentin may be useful in treating mood disorders. This report describes its efficacy and tolerability as an adjunctive agent in treatment-resistant depression. METHODS: A chart review was conducted on 27 outpatients presenting with a depressive disorder in whom gabapentin was added to ongoing treatment with a conventional antidepressant to which patients had not responded after at least 6 weeks. The majority of patients had either prominent anxiety or a history of soft bipolar features, but patients with bipolar I disorder were excluded. Clinical state and adverse effects were assessed retrospectively at each visit. RESULTS: Mean gabapentin trial duration was 15.2+/-7.8 weeks, with a mean final dose of 904+/-445 mg/day (range, 300-1800 mg/day). Clinician-rated measures of clinical state improved significantly from baseline to endpoint. Overall, 37.0% (n=10) of patients were responders at endpoint; another 18.5% (n=5) manifested a transient response not sustained to endpoint. Gabapentin was well tolerated; the most common adverse effects were fatigue, sedation, dizziness, and gastrointestinal symptoms. LIMITATIONS: Treatment was uncontrolled and efficacy assessments were retrospective. CONCLUSION: These findings suggest that gabapentin may be of adjunctive benefit in the management of treatment-resistant depression.     

A review of randomized, controlled clinical trials in acute mania

This review considers the evidence supporting the use of somatic therapies (medications and electroconvulsive therapy) in the treatment of acute mania associated with bipolar disorder. Data from randomized, controlled clinical trials have established the efficacy of lithium, divalproex sodium, and carbamazepine in the treatment of acute mania. The use of combinations of mood stabilizers in the treatment of acute mania has not been well examined in controlled trials. Conventional antipsychotics and some atypical antipsychotics are frequently used as initial or adjunctive treatment. Similarly, benzodiazepines are frequently used as adjunctive agents. Preliminary data suggest that some calcium channel blockers and several anticonvulsants, e.g., lamotrigine, gabapentin, and topiramate, may have therapeutic value in the treatment of acute mania. In contrast, electroconvulsive therapy is generally accepted as being highly effective despite the lack of controlled evidence.     

Synaptic,intracellular, and neuroprotective mechanisms of anticonvulsants: are they relevant for the treatment and course of bipolar disorders?

Treatment of bipolar disorders has progressed significantly in the last decade due to advances in basic and clinical research. Much of this progress has centered on the development of a new generation of mood stabilizers-anticonvulsants. Valproic acid (VPA) and carbamazepine (CBZ) have clear mood stabilizing properties, while lamotrigine (LTG), topiramate (TPM), and gabapentin (GBP) have been investigated to varying degrees. We provide an overview of mechanisms of these potentially mood-stabilizing anticonvulsants, review their commonalities and dissociations to the gold standard non-anticonvulsant mood stabilizer lithium. Regulations of the glutamate excitatory neurotransmission and/or gamma aminobutyric acid (GABA) inhibitory neurotransmission are mostly studied mechanisms of anticonvulsants. The divergent effects of these agents indicate that this mode of action represents initial effect of anticonvulsants in regulating mood. Similar to lithium, intracellular mechanisms of anticonvulsants, primarily VPA and CBZ, include regulation of several protein kinase signaling pathways, leading to regulation of gene expression. Common genes that can be regulated by mood stabilizers are more likely to be the final normalizing components in bipolar disorders. Several anticonvulsants, such as VPA, LTG, and TPM, show neuronal protective function, a commonality with recently identified neuroprotective function of lithium, although the meaning of neuroprotection in bipolar disorders remains to be identified. Understanding the mechanisms of anticonvulsant mood stabilizers, integrated with clinical observations, may ultimately provide important new insights into the pathophysiology and treatment of bipolar disorders.     

Do obese depressed patients respond to topiramate? A retrospective chart review

BACKGROUND: Topiramate, a novel anticonvulsant, has shown promise in preliminary open trials in bipolar disorder, but there are no studies in primary depression. Topiramate's tendency to cause weight loss could be advantageous for many patients with mood disorders. METHODS: A chart review was conducted on 16 female outpatients with a primary major depressive episode and mild to moderate obesity who received open-label adjunctive topiramate. Ongoing psychotropics were continued at previous doses. Self-report symptoms were assessed before and after acute phase (4-8 weeks) treatment in a subset of 11 patients, and clinician ratings were assessed at all visits during extended phase (up to 40 weeks) treatment for the entire group. RESULTS: Patient and clinician symptom ratings dropped significantly during acute phase treatment (5.5+/-1.2 weeks), but only 36% of patients were judged responders. At extended phase endpoint (17.7+/-13.4 weeks), 44% of patients were responders. Body mass index decreased significantly on topiramate, reflecting a mean weight loss of 6.1+/-8.2% from baseline. Central nervous system side effects were prominent. CONCLUSIONS: Topiramate may have potential for the adjunctive treatment of depression in obese patients, but close monitoring of weight and adverse effects is warranted.     

Gabapentin as an adjunctive treatment in bipolar disorder.

OBJECTIVE: To evaluate the efficacy of gabapentin as an adjunctive treatment for bipolar disorder in both depressed and manic phases. METHOD: Thirty seven patients with bipolar type I or II with or without a rapid cycling course were openly treated with gabapentin added to current treatment for up to six months. Mood symptoms were rated weekly for 12 weeks then monthly for 3 months utilizing the HamD and YMS. RESULTS: Participants experienced a significant reduction in both depressive and manic symptoms. CONCLUSIONS: These findings are consistent with others in establishing the efficacy of gabapentin in both phases of bipolar disorder. LIMITATIONS: Small sample size and the use of an open uncontrolled design limit interpretation of results.     

Does adjunctive family therapy enhance recovery from bipolar I mood episodes?

BACKGROUND: Family therapy is sometimes used as adjunctive treatment to pharmacotherapy to help patients recover from mood episodes of bipolar I disorder. However, the efficacy of this practice is not known. METHODS: Ninety-two patients meeting criteria for a current bipolar I mood episode were randomly assigned to family therapy plus pharmacotherapy, multifamily psychoeducational group therapy plus pharmacotherapy, or pharmacotherapy alone. Time to recovery was analyzed with survival analysis. RESULTS: The proportion of subjects within each treatment group who recovered did not significantly differ, nor did time to recovery. LIMITATIONS: The analyses did not include other outcomes such as psychosocial functioning, prophylaxis against recurrences of mood episodes, or compliance with pharmacotherapy. CONCLUSIONS: Neither adjunctive family therapy nor adjunctive multifamily psychoeducational group therapy significantly improves the rate of recovery from mood episodes of bipolar I disorder, compared to treatment with pharmacotherapy alone.     

Relevance of new and newly rediscovered anticonvulsants for atypical forms of bipolar disorder

The so-called atypical forms of bipolar disorder are not a rarity, but instead are rather the rule. Particularly in specialized settings such as the bipolar disorder clinic, the majority of patients are characterized by atypical manifestations (). Mixed states, psychotic mania and a rapid cycling course of bipolar disorder are a challenge both to pharmacological and non-pharmacological treatment. The benefit of classical mood stabilizers such as lithium and carbamazepine is limited in monotherapy, although valproate has a broader spectrum of activity in atypical bipolar disorders and is often used in combination with other agents. Thus, new treatment alternatives are needed urgently for optimizing the treatment of atypical bipolar disorder. During the last decade, several new antiepileptic drugs have been released, e.g. lamotrigine, gabapentin, tiagabine, topiramate and levetiracetam. Others have been available for some time, but only recently have become the focus of bipolar disorder research; for example, phenytoin, and especially, oxcarbazepine. This review will consider our current knowledge of the benefit of these new and newly rediscovered anticonvulsants in treating bipolar disorders, with a special focus on their value in treating atypical manifestations.     

Bipolar mood disorders among Polish psychiatric outpatients treated for major depression

BACKGROUND: Significant proportion of patients treated for depression may have various types of bipolar mood disorders. The aim of the study was to assess the frequency of bipolar disorders among outpatients having at least one major depressive episode, treated by 96 psychiatrists, representing all regions of Poland. METHODS: The study included 880 patients (237 male, 643 female), identified to following diagnostic categories: bipolar I, bipolar II, bipolar spectrum disorder and major depressive disorder. RESULTS: Bipolar mood disorders were found in 61.2% of patients studied, bipolar I more frequent in men and bipolar II in women, and bipolar spectrum in 12% of patients. Patients with age ranges 19-49 and 50-65 years did not differ as to the percentage of diagnostic categories. Patients with bipolar mood disorders compared to major depressive disorder had significantly more frequent family history of bipolar disorder, premorbid hyper- or cyclothymic personality, early onset of depression, symptoms of hypersomnia and hyperphagia, psychotic depression, post-partum depression, and treatment-resistant depression. Bipolar spectrum patients had most clinical features similar to classic types of bipolar disorders. LIMITATIONS: Neither structured interview for family history, nor formal criteria for a number of clinical manifestations were used. The population treated by psychiatrists may not be representative and present a subgroup with more severe mood disorders. CONCLUSIONS: Bipolar mood disorders may be very prevalent among depressive outpatients treated by psychiatrists in Poland, which is confirmed by the results of recent studies. Bipolar patients (including bipolar spectrum) significantly differ from major depressive disorder as to numerous clinical features related mostly to depressive episode.     

Lifetime co-morbidities between social phobia and mood disorders in the US National Comorbidity Survey.

BACKGROUND: General population data were used to study co-morbidities between lifetime social phobia and mood disorders. METHODS: Data come from the US National Comorbidity Survey (NCS). RESULTS: Strong associations exist between lifetime social phobia and major depressive disorder (odds ratio 2.9), dysthymia (2.7) and bipolar disorder (5.9). Odds ratios increase in magnitude with number of social fears. Reported age of onset is earlier for social phobia than mood disorders in the vast majority of co-morbid cases. Temporally-primary social phobia predicts subsequent onset of mood disorders, with population attributable risk proportions of 10-15%. Social phobia is also associated with severity and persistence of co-morbid mood disorders. CONCLUSIONS: Social phobia is a commonly occurring, chronic and seriously impairing disorder that is seldom treated unless it occurs in conjunction with another co-morbid condition. The adverse consequences of social phobia include increased risk of onset, severity and course of subsequent mood disorders. Early outreach and treatment of primary social phobia might not only reduce the prevalence of this disorder itself, but also the subsequent onset of mood disorders.     

Is adjunctive open-label zonisamide effective for bipolar disorder?

OBJECTIVE: To assess the effectiveness and safety of zonisamide in bipolar disorder. METHODS: A chart review was conducted of naturalistic treatment with zonisamide in 35 outpatients meeting DSM-IV criteria for bipolar disorder (9 males, 26 females; mean +/- SD age = 29.2 +/- 12.7; 14 with bipolar disorder type I, 6 with bipolar disorder type II, and 14 with bipolar disorder not otherwise specified). Patients received zonisamide adjunctive therapy between January 1994 and December 2004. Treatment response was defined as a Clinical Global Impressions - Improvement (CGI-I) scale score of +2 (much improved) or + 3 (very much improved). RESULTS: Zonisamide was moderately to markedly effective in 9 subjects (26%). Indication for treatment included depressive (34.3%, [12/35]), manic/hypomanic (28.6%, [10/35]), or mixed (31.4%, [11/35]) symptoms. The mean zonisamide dose was 130 mg/d for a mean duration of treatment of 27.0 +/- 32.3 weeks. Sedation (25%, [4/16]) was the most common side effect; 19/35 (54.3%) reported no side effects. 17/35 (49%) patients terminated early, mostly due to adverse effects (6/35). Using a multivariable model, predictors of response, concurrent mood stabilizers, dose and bipolar subtype (bipolar type I > type II/NOS), were controlled for in this sample. CONCLUSIONS: In 35 persons with bipolar disorder taking standard mood stabilizers and other psychotropic agents, adjunctive zonisamide appears to have modest benefit in global improvement when added to a pre-existing complex medication regimen in patients with bipolar spectrum disorder. These pilot data support the need for larger studies to test the potential efficacy of zonisamide for treatment in mood disorders.     

Maintenance N-acetyl cysteine treatment for bipolar disorder: A double-blind randomised placebo controlled trial

ABSTRACT: BACKGROUND: N-acetyl cysteine (NAC) is a glutathione precursor that has been shown to have antidepressant efficacy in a placebo-controlled trial. The current study aimed to investigate the maintenance effects of NAC following eight weeks of open-label treatment for bipolar disorder. METHOD: The efficacy of a double blind randomized placebo controlled trial of 2 g/day NAC as adjunct maintenance treatment for bipolar disorder was examined. Participants (n = 149) had a Montgomery Asberg Depression Rating Score of [greater than or equal to]12 at trial entry and, after eight weeks of open-label NAC treatment, were randomized to adjunctive NAC or placebo, in addition to treatment as usual. Participants (primarily outpatients) were recruited through public and private services and through newspaper advertisements. Time to intervention for a mood episode was the primary endpoint of the study, and changes in mood symptoms, functionality and quality of life measures were secondary outcomes. RESULTS: There was a substantial decrease in symptoms during the eight-week open-label NAC treatment phase. During the subsequent double-blind phase, there was minimal further change in outcome measures with scores remaining low. Consequently, from this low plateau, between-group differences did not emerge on recurrence, clinical functioning or quality of life measures. CONCLUSIONS: There were no significant between-group differences in recurrence or symptomatic outcomes during the maintenance phase of the trial; however, these findings may be confounded by limitations. Trial Registration The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12607000074493).     

The comorbidity of bipolar and anxiety disorders: prevalence, psychobiology, and treatment issues

BACKGROUND: Although symptoms of anxiety as well as anxiety disorders commonly occur in patients with bipolar disorder, the pathophysiologic, theoretical, and clinical significance of their co-occurrence has not been well studied. METHODS: The epidemiological and clinical studies that have assessed the overlap of bipolar and anxiety disorders are reviewed, with focus on panic disorder and obsessive-compulsive disorder (OCD), and to a lesser extent, social phobia and post-traumatic stress disorder. Potential neural mechanism and treatment response data are also reviewed. RESULTS: A growing number of epidemiological studies have found that bipolar disorder significantly co-occurs with anxiety disorders at rates that are higher than those in the general population. Clinical studies have also demonstrated high comorbidity between bipolar disorder and panic disorder, OCD, social phobia, and post-traumatic stress disorder. Psychobiological mechanisms that may account for these high comorbidity rates likely involve a complicated interplay among various neurotransmitter systems, particularly norepinephrine, dopamine, gamma-aminobutyric acid (GABA), and serotonin. The second-messenger system constituent, inositol, may also be involved. Little controlled data are available regarding the treatment of bipolar disorder complicated by an anxiety disorder. However, adequate mood stabilization should be achieved before antidepressants are used to treat residual anxiety symptoms so as to minimize antidepressant-induced mania or cycling. Moreover, preliminary data suggesting that certain antimanic agents may have anxiolytic properties (e.g. valproate and possibly antipsychotics), and that some anxiolytics may not induce mania (e.g. gabapentin and benzodiazepines other than alprazolam) indicate that these agents may be particularly useful for anxious bipolar patients. CONCLUSIONS: Comorbid anxiety symptoms and disorders must be considered when diagnosing and treating patients with bipolar disorder. Conversely, patients presenting with anxiety disorders must be assessed for comorbid mood disorders, including bipolar disorder. Pathophysiological, theoretical, and clinical implications of the overlap of bipolar and anxiety disorders are discussed.     

Gabapentin treatment of the non-refractory bipolar spectrum: an open case series

OBJECTIVE: To determine if gabapentin is effective in monotherapy or add-on treatment of non-refractory bipolar disorder in open prospective treatment. METHODS: Charts of 21 outpatients meeting DSM-IV criteria for bipolar spectrum disorder (type I, type II, NOS, and cyclothymia) and who were treated with gabapentin were reviewed and clinical response was assessed based on prospective application of the Hamilton Depression Rating Scale (HDRS), the Young Mania Rating Scale (YMRS), the Clinical Global Impression scale (CGI), and the Global Assessment of Functioning scale (GAF). Also, response was rated retrospectively using the Clinical Global Impression scale for Bipolar Disorder (CGI-BP). RESULTS: Eight patients received gabapentin monotherapy and 13 received adjunctive therapy. Similar improvement in depression was noted in the monotherapy group, without induction of mania. Gabapentin was associated with a 43.8% improvement in manic symptoms and a 27.6% improvement in depressive symptoms in the overall sample. In the depressed subsample (n=10), there was a 57.5% improvement in depressive symptoms (P=0.10). Using the CGI-BP, gabapentin was moderately to markedly effective in 43% of patients for overall bipolar illness, 38% for depressive symptoms, and 25% for manic symptoms. Of those in the study, 62% reported side effects, mainly sedation and nausea, with 14% of the total sample discontinuing treatment due to adverse events. CONCLUSIONS: Gabapentin, either alone or as an adjunct, appeared moderately effective in treating depression in this small, uncontrolled, heterogeneous sample of non-refractory bipolar spectrum illness. Coupled with the earlier clinical literature, these data suggest the need for prospective double-blind studies of depressive illness in the bipolar spectrum.     

Lamotrigine for the treatment of bipolar disorder: a clinical case series.

BACKGROUND: Recently, a number of new agents have become available to treat bipolar disorder, however many patients may not respond fully even when used in combination. Early reports in epilepsy studies suggested mood-related effects of lamotrigine treatment, as have preliminary reports in bipolar patients. METHODS: Seventeen patients meeting DSM-IV criteria for bipolar I (n = 9) or bipolar II (n = 8) disorder displaying affective symptoms and a past history of inadequate response or tolerability to at least two standard mood stabilizing agents were recruited through the Stanley Foundation Bipolar Network and treated with the new anticonvulsant lamotrigine in an add-on, open-label study. Response to therapy was assessed using the Clinical Global Impression Scale modified for bipolar disorder. RESULTS: The mean dose of lamotrigine was 187+/-157 mg/day (range 50-600 mg/day) for a mean duration of 159+/-109 days (range 14-455 days). Eleven (65%) patients were rated as very much or much improved. Lamotrigine was well tolerated, and may have mood stabilizing and antidepressant properties in some patients with bipolar disorder. LIMITATIONS: The study is hypothesis generating because it was uncontrolled and open. Controlled studies are warranted. CONCLUSIONS: This preliminary report supports clinical improvement for both mood cycling and depression in patients with bipolar disorder treated with lamotrigine.     

Is bipolar disorder still underdiagnosed? Are antidepressants overutilized?

BACKGROUND: Previous studies have suggested that bipolar disorder may be underdiagnosed, and that antidepressants may be over-utilized in its treatment. METHODS: Consecutively admitted patients (n =48) diagnosed with DSM-IV bipolar disorder, type I, (n = 44) or schizoaffective disorder, bipolar type, (n = 4) were interviewed systematically and their charts were reviewed to confirm diagnosis before admission. They were then treated according to systematic structured interview diagnoses. These data reflect the changes in diagnoses and treatment. RESULTS: 40% (19/48) were identified with previously undiagnosed bipolar disorder, all previously diagnosed with unipolar major depressive disorder. A period of 7.5+/-9.8 years elapsed in this group before bipolar diagnosis was made. Antidepressant use was high on admission (38%) and was reduced with acceptable treatment response rates. The adjunctive use of risperidone appeared to be a good treatment alternative. LIMITATIONS: While diagnoses were made prospectively, treatment response was assessed retrospectively, and was based on non-randomized, naturalistic therapy. CONCLUSIONS: Systematic application of DSM-IV criteria identified previously undiagnosed bipolar disorder in 40% of a referred population of patients with mood disorders, all previously misdiagnosed as unipolar major depressive disorder. Antidepressants appeared overutilized and risperidone was an effective alternative adjunctive therapy agent.     

Comorbid bipolar disorder and premenstrual dysphoric disorder: real patients, unanswered questions

Large-scale clinical and epidemiological studies suggest a link between bipolar disorder (BD) and premenstrual dysphoric disorder (PMDD). However, smaller studies using prospective charting failed to find this association. Here, we report three cases of individuals with BD and comorbid PMDD who responded successfully to adjunctive contraceptive agents in the management of their severe premenstrual symptoms. While controlled trials investigating pharmacological and non-pharmacological treatments are awaited, adjunctive treatment of contraceptive agents and mood stabilizers may be an option in the treatment of comorbid BD and PMDD.     

Lithium,anticonvulsants and suicidal behavior in bipolar disorder

BACKGROUND: Lithium has been found to be effective in reducing suicide rates during long term treatment of patients with bipolar disorders. Data on the efficacy of anticonvulsant mood stabilizers in reducing suicide risk are sparse. METHOD: Charts of 140 bipolar patients treated continuously for a minimum of 6 months during a 23-year period of private practice by the senior author were extracted from nearly 4000 patient records. Data extracted from the charts were incidence of completed suicide, number of suicide attempts, and number of hospitalizations for suicidal ideation or behavior per 100 patient-years of either 'on' or 'off' lithium or anticonvulsant mood stabilizer monotherapy. RESULTS: Only one completed suicide (during a period off of lithium) occurred in the patients studied. Incidence of non-lethal suicidal behavior was not different during treatment with lithium, compared with anticonvulsants. Being on a mood stabilizer significantly protected against suicidal behavior. The relative protective effect was more modest than in reports from other treatment settings. LIMITATIONS: This was a retrospective chart review study of naturalistically treated patients. CONCLUSIONS: Treatment of patients with bipolar disorder with either lithium or anticonvulsant mood stabilizers was associated with reduced risk of suicidal behavior. This study did not find evidence for a difference in the protective effect of the two types of mood stabilizing medications against non-lethal suicidal behavior in the naturalistic setting of private practice.     

A closer look at treatment resistant depression: is it due to a bipolar diathesis?

BACKGROUND: Treatment resistant depression is a common clinical problem. Studies have shown that a large number of patients with depression do not have a satisfactory clinical outcome in spite of adequate trials of antidepressant drugs. In this study, we investigated demographic and clinical characteristics, diagnostic subtypes, and illness outcome of patients with resistant depression and a history of escape of response to adequate trials of at least two antidepressants for a previous episode. METHOD: Sixty-one patients who were seen consecutively at a mood disorders clinic with the diagnosis of "unipolar" treatment resistant depression, and followed up for at least one year, were interviewed using the Structured Clinical Interview for DSM-IV. Prospectively collected data including the occurrence of episodes of hypomania, and supplemental information from family members on illness course were also used for purposes of diagnostic re-evaluation. RESULTS: At intake, 35% of the patients were diagnosed as having a bipolar disorder. At follow-up, there was a 59% prevalence of bipolar disorder. Of the patients with major depressive disorder, 52% were subsequently classified as having bipolar spectrum disorder. The most important finding was that 80% of patients were found to show evidence of bipolarity. Moreover, the most common change in medication was a switch to mood stabilizers. CGI ratings showed significant improvement in functioning from the time of initial consultation. LIMITATIONS: This was a naturalistic study, and the data were collected in a non-blind fashion. CONCLUSIONS: The findings suggest that the majority of cases of unipolar treatment resistant depression, occurring in the context of loss of antidepressant response, have a bipolar diathesis.     

Use of topiramate, a new anti-epileptic as a mood stabilizer

Rationale: Because some anti-epileptic drugs (AEDs) are effective in bipolar affective disorders, the new AED topiramate (TPM) may be effective in psychiatric illnesses. TPM was evaluated in mood disorders refractory to previous therapies including newer AEDs. Methods: Charts of 58 consecutive patients, 39 outpatients (15 males, 24 females) and 19 inpatients (6 males, 13 females) were reviewed. TPM 25 mg. b.i.d. was added to existing therapy and titrated in 50 mg increments every 3–7 days. Improvement was rated on a Likert global assessment scale of marked, moderate, mild, or no improvement or worse, based on quality of sleep, appetite, mood, and concentration. Results: Of the 58 patients with psychiatric disorders, 44 patients had rapid cycling bipolar disorders characterized by manic, hypomanic, or mixed episodes. Eighteen patients had previously failed to respond to lamotrigine and/or gabapentin in addition to conventional mood stabilizers. Fourteen were Bipolar I, six Bipolar II, and seven mixed, ten patients had cyclothymic disorder, seven had bipolar disorder not otherwise specified. Of the remaining 14 patients, nine had schizoaffective disorder, three patients had dementia and two had psychosis. Mean duration of TPM treatment was 16.0 weeks; mean TPM dosage approximately 200 mg/day. Thirty-six of 58 (62%) patients exhibited marked or moderate improvement, usually within days or weeks. Twenty-three of 44 (52%) patients with bipolar affective disorders showed marked or moderate improvement. Minimal/no improvement was observed in 16; six were rated as worse. Adverse events included delirium in one patient with Bipolar Disorder Type I who overmedicated with TPM (800 mg) and tranylcypromine sulfate (170 mg) combined with alcohol. Other adverse effects were minor and included: paresthesias, somnolence, fatigue, impaired concentration and memory, nausea, and diarrhoea. Limitations: This study was performed in a nonrandom open and retrospective fashion. Therefore, any findings are limited by the design of this study. Conclusion: TPM may be useful in patients with mood disorders unresponsive to traditional therapy and warrants further clinical investigation.     

Combined Psychotherapy and Pharmacotherapy for Mood and Anxiety Disorders in Adults: Review and Analysis

Studies suggest a complex relationship between cognitive-behavior therapy (CBT) and pharmacotherapy for the combined treatment of mood disorders and anxiety disorders. Combined treatment for depression may have beneficial effects when applied to patients with chronic depression and in cases to prevent relapse. In bipolar disorder there is evidence for a strong effect of psychosocial treatment on the course of the disorder. In the anxiety disorders, there are some benefits in the short term, but combined treatment may limit the maintenance of treatment gains offered by CBT alone. Combined treatment should not be considered the default treatment for mood and anxiety disorders, with the possible exception of bipolar disorder. Instead, decisions whether combined treatment is worth the added cost and effort should be made in relation to the disorder under treatment, the level of severity or chronicity, and the stage of treatment (e.g., acute vs. relapse prevention).