Comparison of the efficacy between paroxetine and sertraline augmented with aripiprazole in patients with refractory major depressive disorder

Objective

Only two-thirds of depressive patients respond to antidepressant treatment. In recent years, addition of an atypical antipsychotic drug to ongoing treatment with an antidepressant has been considered effective and well-tolerated. In the present study, we compared the efficacy between paroxetine and sertraline augmented with aripiprazole in patients with refractory major depression.

Subjects and methods

Twenty-four patients who met the DSM-IV criteria for major depressive disorder who did not at least two different classes of antidepressants were enrolled in the study. Nine were male and thirteen were female, and their ages ranged from 28 to 66 (mean ± SD = 39 ± 12) years. Patients were prescribed paroxetine (n = 11) or sertraline (n = 13) for 4 weeks. Then, those whose scores on the 17-item Hamilton Rating Scale for Depression (HAMD17) decreased below 50% received adjunctive therapy of aripiprazole for 4 weeks.

Results

Although the use of either combination treatment decreased the HAMD17 scores compared to the respective monotherapy, there was no significant difference in HAMD17 scores between the paroxetine plus aripiprazole group and sertraline plus aripiprazole group.

Conclusion

Aripiprazole augmentation therapy with paroxetine or sertraline was equally effective and tolerated in patients with refractory major depressive order.     

Topiramate augmentation in patients with resistant major depressive disorder: a double-blind placebo-controlled clinical trial

Background

Despite evolution of new antidepressant treatment, clinicians still encounter challenges in the treatment of depressed patients. Looking for new medications that can potentiate the effects of current antidepressants seems to be necessary. Our objective is to survey the efficacy of topiramate augmentation in resistant major depressive disorder (MDD).

Method

This augmentation trial was designed as an 8-week randomized, placebo-controlled, double-blind study. Fifty three patients with DSM-IV diagnosis of MDD who had failed to respond to at least 8 weeks of treatment with an adequate dose of one of the SSRIs (fluoxetine, citalopram or serteraline) were included in the study. Patients were randomized to receive a flexible dose of topiramate (100-200 mg/day) or placebo beside their current antidepressant medication for a period of eight weeks. Outcome measures were Hamilton Depression Scale (HAM-D) and Clinical Global Impression (CGI).

Results

42 patients completed the study and there were 6 and 5 dropouts in topiramate and placebo groups, respectively. The topiramate group demonstrated significant improvement over the study period based on mean HAM-D score at week 8 compared to baseline (P = .000, Z = 3.699). Those receiving topiramate demonstrated to have a mean decrease of 32.0% in HAM-D score, compared to only 5.5% for those receiving placebo. Depressed mood, suicidality, insomnia (early, middle and late), agitation and anxiety symptoms were significantly improved in the topiramate group.

Conclusion

Our double-blind placebo-controlled study demonstrated that topiramate augmentation potentiate the efficacy of selective serotonin reuptake inhibitors (SSRIs) in treatment of resistant major depressive disorder. Of note is that our study is preliminary and larger double-blind studies are needed to confirm the results.     

Aripiprazole augmentation of antidepressants for the treatment of partially responding and nonresponding patients with major depressive disorder

OBJECTIVE: To determine the efficacy and tolerability of aripiprazole, a dopamine D2 and 5-HT1A receptor partial agonist, as augmentation of antidepressant treatment of partially responding and nonresponding patients with major depressive disorder. METHOD: Fifteen patients with major depressive disorder (diagnosed with a site-generated form described in the text) and an incomplete response or no response to > or = 8 weeks of antidepressant (selective serotonin reuptake inhibitor, venlafaxine, or bupropion) monotherapy were treated with aripiprazole augmentation in an 8-week, open-label study. Data were gathered from July 2003 to March 2004. RESULTS: The mean duration of antidepressant monotherapy at baseline was 43.1 weeks. At baseline, mean Clinical Global Impressions-Severity of Illness scale and Hamilton Rating Scale for Depression (HAM-D) scores were 4.3 and 18.9, respectively. After initiation of aripiprazole augmentation, 6 of 15 patients achieved remission (HAM-D score < or = 7) at week 1, and 9 of 15 patients remitted by week 2. All 8 completers achieved remission by study endpoint. Akathisia in 2 patients who withdrew prematurely prompted a reduction in the starting dose of aripiprazole from 10 mg/day to 2.5 mg/day, resulting in a 50% reduction in attrition due to akathisia (2/7 withdrew due to akathisia with the 10-mg starting dose, 1/8 withdrew due to akathisia with the 2.5-mg starting dose). Discontinuation rates after 4 weeks of treatment were lower for the 2.5-mg starting dose (1/8 patients) than for the 10-mg starting dose (3/7 patients). Overall discontinuation rates at endpoint were lower for the 2.5-mg dose (3/8 patients) than the 10-mg dose (4/7 patients). Response to aripiprazole augmentation did not appear to be related to the antidepressant used at study initiation. CONCLUSION: Aripiprazole is an effective augmentation strategy for improving therapeutic response in patients with treatment-resistant major depressive disorder when administered in combination with standard antidepressant therapy. Based on this clinical signal, a double-blind, placebo-controlled trial is warranted.     

Adding a low dose atypical antipsychotic drug to an antidepressant induced a rapid increase of plasma brain-derived neurotrophic factor levels in patients with treatment-resistant depression

Only two-thirds of depressive patients respond to antidepressant treatment. Recently, addition of an atypical antipsychotic drug to ongoing treatment with an antidepressant has been considered effective and well-tolerated. In the present study, we examined the effects of various atypical antipsychotic drugs as adjuvant to antidepressants, including selective serotonin reuptake inhibitors (SSRIs), serotonin noradrenaline reuptake inhibitors, tricyclic antidepressants and mood stabilizers, on plasma BDNF levels in refractory depressed patients. Forty-five patients who met the DSM-IV criteria for major depressive disorder (n = 31) or bipolar disorder (10 with bipolar I, 4 with bipolar II) were enrolled in the study. Twenty-one were male and 24 were female, and their ages ranged from 28 to 71 (mean ± SD = 49 ± 12) years. Plasma BDNF levels were measured using a sandwich ELISA. The plasma BDNF levels in responders (those showing a decline in HAM-D scores of 50% or more) were significantly increased 4 weeks after the administration of each atypical antipsychotic drug, while the levels in non-responders were not changed. Furthermore, there was a significant correlation between the changes in HAM-D scores and the changes in plasma BDNF levels. These results suggest that adding an atypical antipsychotic drug to ongoing treatment with an antidepressant or mood stabilizer is useful and well-tolerated for refractory depressed patients, and the efficacy of atypical antipsychotics as an adjuvant might involve an increase of plasma BDNF levels.     

Is switching antidepressants following early nonresponse more beneficial in acute-phase treatment of depression?: a randomized open-label trial

Rationale

Treatment guidelines for major depressive disorder (MDD) recommend a continuous use of antidepressants for several weeks, while recent meta-analyses indicate that antidepressant efficacy starts to appear within 2 weeks and early treatment nonresponse is a predictor of subsequent nonresponse.

Objectives

We prospectively compared 8-week outcomes between switching antidepressants and maintaining the same antidepressant in early nonresponders, to generate a hypothesis on possible benefits of early switching strategy.

Method

Patients with MDD without any treatment history for the current episode were included. When subjects failed to show an early response (i.e., ≥ 20% improvement in the Montgomery-Åsberg Depression Rating Scale (MADRS)) to the initial treatment with sertraline 50 mg at week 2, they were randomly divided into two groups; in the Continuing group, sertraline was titrated at 50-100 mg, whereas sertraline was switched to paroxetine 20-40 mg in the Switching group. A primary outcome measure was a response rate (i.e., ≥ 50% improvement in the MADRS) at week 8.

Results

Among 132 subjects, 41 subjects showed early nonresponse. The Switching group (n = 20) showed a higher rate of responders than the Continuing group (n = 21) (75% vs. 19%: p = 0.002). Further, the Switching group was also superior in the rate of remitters (total score of ≤ 10 in the MADRS) (60% vs. 14%: p = 0.004) and continuous changes in the MADRS (19.0 vs. 7.5: p < 0.001).

Conclusions

Our preliminary findings suggest that patients with MDD who fail to show early response to an initial antidepressant may derive benefits from the early switching antidepressants in the acute-phase treatment of depression.     

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

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.     

Tryptophan hydroxylase 2 gene is associated with major depression and antidepressant treatment response

Tryptophan hydroxylase-2 (TPH2) is the rate-limiting biosynthetic isoenzyme for serotonin that is preferentially expressed in the brain and has been implicated in the pathogenesis of major depressive disorder (MDD) and in the mechanism of antidepressant action. This study aimed to investigate whether common genetic variation in the TPH2 gene is associated with MDD and therapeutic response to antidepressants in a Chinese population. A total of 508 MDD patients and 463 unrelated controls were recruited. Among the MDD patients, 187 accepted selective serotonin reuptake inhibitor (fluoxetine or citalopram) antidepressant treatment for 8 weeks with therapeutic evaluation before and after treatment. Five TPH2 polymorphisms were genotyped and their association with MDD or treatment response was assessed by haplotype and single-marker analysis. In single-marker-based analysis, the rs17110747-G homozygote polymorphism was found to be more frequent in the MDD patients than in the controls (P = 0.002). Genotype analysis in responders (defined as those with a 50% reduction in baseline Hamilton score) and non-responders after 8 weeks of antidepressant treatment showed that the proportion of rs2171363 heterozygote carriers was higher in the responders than the non-responders (P = 0.009). No significant association with MDD or antidepressant therapeutic response was discovered in haplotype analyses. Our findings show that TPH2 genetic variants may play a role in MDD susceptibility and in acute therapeutic response to selective serotonin reuptake inhibitors.     

Aripiprazole augmentation versus antidepressant switching for patients with major depressive disorder: A 6-week,randomized, rater-blinded,prospective study

No study has directly compared the efficacy and tolerability of aripiprazole augmentation (AA) and antidepressant switching (SW) in patients with major depressive disorder (MDD). This is the first 6-week, randomized, rater-blinded, direct comparison study between AA and SW in outpatients. An inadequate response to antidepressants was defined as a total score ≥14 on the Hamilton Depression Rating Scale-item 17 (HDRS-17) despite adequate antidepressant dosage for at least 6 weeks in the current depressive episode. The primary endpoint was change in the total score of the Montgomery–Åsberg Depression Rating Scale (MADRS) from baseline to the end of treatment. Secondary efficacy measures included the response and remission rates as priori defined at the end of treatment: changes in total scores of the HDRS-17, Iowa Fatigue Scale (IFS), and Sheehan Disability Scale (SDS) from baseline to the end of treatment and the proportion of patients who scored 1 or 2 on the Clinical Global Impression-Improvement Score (CGI-I) at the end of treatment. Tolerability was assessed with the Barnes Akathisia Rating Scale (BARS) and Arizona Sexual dysfunction scale (ASEX), and the numbers of adverse events were compared between the two groups. A total of 101 patients were randomized to either AA (n = 52) or SW (n = 49). The mean change in the MADRS score from baseline was significantly higher in the AA, with a difference in magnitude of −8.7 (p < 0.0001). The intergroup difference was first evident in week 2. The numbers of responders (p = 0.0086) and remitters (p = 0.0005) were also significantly higher in the AA (60% and 54%, respectively) compared with the SW (32.6% and 19.6%, respectively). On most secondary endpoints, AA showed better clinical outcomes compared to SW. The tolerability profiles were comparable between the two groups. Overall, AA yielded potentially beneficial clinical outcomes compared to SW. Given the methodological shortcomings of the present study, adequately powered, more rigorously controlled clinical trials are strongly warranted to confirm the present findings.     

A randomized, placebo-controlled trial of risperidone augmentation for patients with difficult-to-treat unipolar, non-psychotic major depression

Objective

Patients (30-50%) with non-psychotic major depression will not respond despite an adequate trial of antidepressant medication. This study evaluated risperidone as an augmenting agent for patients who failed or only partially responded to an adequate trial of an antidepressant medication.

Method

Ninety-seven patients with unipolar non-psychotic major depression who were not responsive to antidepressant monotherapy were randomized to risperidone (0.5-3 mg/day) or placebo augmentation in a four-week, double-blind, placebo controlled treatment trial. The primary outcome measure was remission defined by a score of ?10 on the Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes measures were the Hamilton Rating Scale for Depression, the Clinician Global Impression of Severity scale and the overall satisfaction item of the Quality of Life and Enjoyment Questionnaire.

Results

Subjects in both treatment groups improved significantly over time. The odds of remitting were significantly better for patients in the risperidone vs. placebo arm (OR = 3.33, p = .011). At the end of 4 weeks of treatment 52% of the risperidone augmentation group remitted (MADRS ? 10) compared to 24% of the placebo augmentation group (CMH(1) = 6.48, p = .011), but the two groups were converging. Patients in the risperidone group also reported significantly more improvement in quality-of-life than patients in the placebo group. There were no between-group differences in the number of adverse events reported, however, weight gain was significantly higher in the group receiving risperidone.

Conclusion

Augmentation of an antidepressant with risperidone for patients with difficult-to-treat depression leads to more rapid response and a higher remission rate and better quality-of-life.     

A benzisothiazole derivative and antipsychotic agent,perospirone, for augmentation of selective serotonin reuptake inhibitors (SSRIs) in refractory obsessive-compulsive disorder (OCD): two patient case series

Even though selective serotonin reuptake inhibitors (SSRIs) are the mainstay of pharamacological treatment for obsessive-compulsive disorder (OCD), as many as 40% of patients do not have an adequate response to these medications. For such SSRI-refractory patients, the augmentation of SSRIs with new-generation antipsychotics that modulate both 5-HT and DA systems has recently been proven effective in controlled augmentation studies. The benzisothiazole derivative perospirone is a new serotonin 5-HT2 and dopamine D2 antagonist available in Japan for the treatment of schizophrenia. As its unique property, perospirone also exhibits 5-HT1A agonistic action. We present two SSRI-refractory OCD patients who showed little improvement with adequate trials of SSRI monotherapy, but exhibited significant improvement in their OCD symptoms after the addition of perospirone to ongoing SSRI treatment. The cases suggest that perospirone augmentation may be an effective and well-tolerated strategy for SSRI-refractory OCD patients. Controlled studies are required to further confirm the efficacy and tolerability of perospirone augmentation for treatment-resistant OCD.     

Reduced platelet BDNF level in patients with major depression

Serum and plasma brain-derived neurotrophic factor (BDNF) levels as well as brain BDNF have previously been shown to be decreased in patients with major depressive disorder (MDD). We explored whether platelet BDNF levels, circulating stored BDNF, would be lower in MDD patients than in normal controls. BDNF levels were examined in platelet-rich plasma (PRP) and platelet-poor plasma (PPP) in 20 hospitalized non-suicidal MDD patients, 20 recent-suicidal MDD patients, and 20 normal controls. Platelet BDNF content was calculated by subtracting PPP BDNF level from PRP BDNF level, and dividing the result by the total platelet count, and it was expressed as pg/10⁶ platelets. Individuals were evaluated using a Structured Clinical Interview for DSM-IV and a Hamilton Depression Rating Scale. Platelet BDNF contents were significantly lower in non-suicidal patients (3.09 ± 2.53 pg/10⁶ platelets) and recent-suicidal MDD patients (3.16 ± 1.99 pg/10⁶ platelets) than in healthy controls (6.17 ± 2.64 pg/10⁶ platelets) (p < 0.01). However, platelet BDNF contents had no significant differences between non-suicidal and recent-suicidal patients. PRP BDNF levels were also significantly lower in non-suicidal and suicidal MDD patients than in healthy controls (p = 0.029), while PPP BDNF had no significant difference between 3 groups (p = 0.971). Our findings suggest that there is a decrease in the platelet BDNF of patients with major depression. Reduced platelet BDNF contents as circulating stored BDNF could be associated with lower serum BDNF level in patients with major depression.     

Perospirone augmentation of paroxetine in treatment of refractory obsessive-compulsive disorder with depression

Obsessive-compulsive disorder (OCD) is often complicated by depression. We report on a patient with treatment-refractory OCD and treatment-refractory major depression who demonstrated a robust response to augmentation of paroxetine with perospirone. Perospirone is a second-generation antipsychotic agent with antagonist effects on both serotonin 5-HT(2A) and dopamine D(2) receptors, as well as a unique agonist effects on serotonin 5-HT(1A) receptors. Future studies would be valuable to elucidate the utility of augmentation therapy of selective serotonin reuptake inhibitors with perospirone in the treatment of refractory OCD with depression.     

The brain-derived neurotrophic factor (BDNF) polymorphism Val66Met is associated with neither serum BDNF level nor response to selective serotonin reuptake inhibitors in depressed Japanese patients

Background

We investigated the relationship between a brain-derived neurotrophic factor (BDNF) polymorphism (Val66Met) and the clinical response of patients with major depressive disorder to selective serotonin reuptake inhibitors (SSRIs; here, paroxetine and sertraline). In addition, serum BDNF levels in these patients were considered together with the clinical response.

Methods

A total of 132 patients who met the DSM-IV criteria for major depressive disorder were enrolled in the study. 54 of these patients were male and 78 were female (age range, 20-74 years; mean ± S.D., 51 ± 15). The patients' clinical improvement was evaluated using the 17-item Hamilton Rating Scale for Depression (HAMD-17) before (T0) and at 8 weeks after the administration of SSRI treatment (T8). Patients with at least a 50% decrease in the HAMD-17 score were classified as responders.

Results

No correlation was observed between the BDNF Val66Met polymorphism and response to SSRIs or between the BDNF Val66Met polymorphism and serum BDNF levels at T0. An inverse correlation was found between serum BDNF levels and HAMD-17 scores at T0.

Conclusions

These results suggest that the BDNF Val66Met polymorphism is independent of both the response to SSRI treatment and serum BDNF levels. The findings in the present study reconfirm that the serum BDNF level is a state biomarker for depression.     

Reduced antioxidant defense systems in schizophrenia and bipolar I disorder

Numerous evidence and proofs suggest that the oxidative stress contributes to the pathogenesis of schizophrenia (SZ) and bipolar disorder (BD). The aim of this study is to determine the glutathione levels and the antioxidant enzyme activities in blood samples of patients suffering from SZ and patients with bipolar disorder in comparison with the healthy controlled subjects. It was a case-controlled study carried on upon three groups: forty-six SZ patients (41 men and 5 women, mean age = 33.2 ± 7 years), thirty BD patients (25 men and 5 women, mean age = 31.3 ± 8 years) and forty healthy controls (33 men and 7 women, mean age = 32.3 ± 7 years).     

The wide variability of perospirone metabolism and the effect of perospirone on prolactin in psychiatric patients

Background

Perospirone was developed in Japan and is used for the treatment of schizophrenia and related illnesses. The authors investigated the relationship between the dosage of perospirone and the plasma levels of perospirone and its active metabolite, ID15036, and also evaluated the impact of the plasma concentrations of perospirone and ID15036 on the plasma prolactin level to examine whether perospirone or ID15036 affected the dopamine D₂ blockade, in psychiatric patients treated with perospirone.

Methods

The subjects consisted of 21 adults treated with perospirone (4–60 mg/day). The plasma perospirone and ID15036 levels were measured in 21 patients and serum prolactin levels were investigated in 10 male patients with schizophrenia.

Results

The plasma ID15036 level was higher than the plasma perospirone, and a positive correlation was observed between the dosage of perospirone and the ID15036 levels (p = 0.032). The 10 male patients showed a positive correlation between the plasma perospirone levels and plasma prolactin levels (r = 0.688, p = 0.028) and between the plasma ID15036 levels and prolactin levels (r = 0.775, p = 0.009).

Conclusion

The plasma levels of ID15036 may have a greater impact on the dopamine D₂ blockade than perospirone in patients treated with perospirone.     

The loudness dependence of the auditory evoked potential (LDAEP) in schizophrenia,bipolar disorder,major depressive disorder,anxiety disorder,and healthy controls

Background

Serotonergic dysfunction in schizophrenia, bipolar disorder, major depressive disorder, anxiety disorder, and healthy controls was evaluated by measuring the activity of the loudness dependence of the auditory evoked potential (LDAEP).

Methods

The 357 subjects who were evaluated comprised 55 normal controls, 123 patients with major depressive disorder, 37 with bipolar disorder, 46 with schizophrenia, 37 with panic disorder (PD), 31 with generalized anxiety disorder (GAD), and 28 with post-traumatic stress disorder (PTSD).

Results

LDAEP was significantly stronger in healthy controls than in patients with either bipolar disorder (p = 0.025) or schizophrenia (p = 0.008), and significantly stronger in patients with major depressive disorder than in those with bipolar disorder (p = 0.01) or schizophrenia (p = 0.03). LDAEP did not differ significantly between patients with major depressive disorder and healthy control subjects (p = 0.667), or between healthy control subjects and patients with anxiety disorder, including PD (p = 0.469), GAD (p = 0.664), and PTSD (p = 0.167).

Conclusion

The findings of the present study reveal that patients with major psychiatric disorders exhibit different strengths of LDAEP according to their serotonin-related pathology. Studies controlled for psychotropic medication, menstruation cycle, and smoking are needed.     

Effects of antidepressants on plasma metabolites of nitric oxide in major depressive disorder: Comparison between milnacipran and paroxetine

Depression is a risk factor for coronary heart disease (CHD). It has been demonstrated that there is a potential role of nitric oxide (NO) in the relationship between depression and CHD risk as well as an effect of antidepressants on NO production. This study included 40 in- or outpatients in our university hospital who met the DSM-IV-TR criteria for major depressive disorder (M/F: 15/25, age: 47 ± 19 years) and 30 age- and sex-matched healthy controls (M/F: 10/20, age: 45 ± 15 years), and also examined the effects of the antidepressants on the plasma NOx levels in depressed patients. The baseline plasma NOx levels were significantly lower in the whole depressed group than in the control group (p < 0.01). Treatment with milnacipran, but not paroxetine, significantly increased the plasma NOx levels by 4 and 8 weeks. These results suggest that decreased plasma NOx levels might be partially associated with the pathophysiology of depression, and that treatment with milnacipran, a serotonin noradrenaline reuptake inhibitor, might increase those levels in depressed patients.     

No predictors of antidepressant patient response to milnacipran were obtained using the three-factor structures of the Montgomery and Asberg Depression Rating Scale in Japanese patients with major depressive disorders

Aims:  Milnacipran, a new specific serotonin and norepinephrine re-uptake inhibitor, is as effective as tricyclic antidepressants. Symptomatological predictors of antidepressant response to milnacipran have not been studied until now.
Methods:  This study included 101 Japanese patients who fulfilled the DSM-IV criteria for the diagnosis of major depressive disorders and whose score on the Montgomery and Åsberg Depression Rating Scale (MADRS) was ≥21. Eighty-three patients were finally included. Patients with a pretreatment MADRS score ≥31 points were defined as severe ( n  = 28), and the rest as non-severe ( n  = 55). The three-factor model of MADRS was used for analysis; the first factor was defined by three items, the second factor was defined by four items and the third factor was defined by three items representing dysphoria, retardation, and vegetative symptoms, respectively. Milnacipran was administered twice daily for 6 weeks. The initial dose was 50 mg/day; after a week it was increased to 100 mg/day.
Results:  No significant difference was observed in the mean score of first factor, second factor and third factor at pretreatment time between responders and non-responders in both severe and non-severe patients.
Conclusions:  No predictor of antidepressant response to milnacipran was obtained using the three-factor structures of the MADRS in Japanese patients with major depressive disorders.     

Accelerating response to antidepressant treatment in depression: A review and clinical suggestions

Objective

The primary objective of this article is to review the literature regarding the speed of response to antidepressant drugs and potential strategies to accelerate the antidepressant response in new antidepressant-free patients with depression. Based on these data, we try to propose both an effective and safe antidepressant treatment strategy to alleviate depressive symptoms at the earliest opportunity.

Data sources

Data were identified by searches of Medline (1966 to September 2009) and references from relevant articles and books. Search terms included depression, antidepressant, predictor, response, onset, acceleration, and augmentation. As our focus was on the acute phase treatment of depression, articles relevant to treatment-resistant depression were excluded. Only articles written in English or Japanese were consulted.

Data selection

Studies, reviews, and books pertaining to the treatment of depression with a special regard to accelerating therapeutic effects were selected.

Data synthesis

Most of the available treatment guidelines for major depressive disorders recommend the continuous use of antidepressants for 4 to 8 weeks based on the idea of a delayed onset of response to these drugs. Contrary to this conventional belief, the recent data indicate that antidepressants start to exert their effects within 2 weeks and early non-response could predict a subsequent unfavorable outcome.

Conclusions

These findings suggest the need of revisiting the timing of an antidepressant switch for early non-responders, whereby switching could be commenced in as early as 2 weeks.     

Increased serum levels of high mobility group box 1 protein in patients with autistic disorder

Background

High mobility group box 1 (HMGB1) is a highly conserved, ubiquitous protein that functions as an activator for inducing the immune response and can be released from neurons after glutamate excitotoxicity. The objective of the present study was to measure serum levels of HMGB1 in patients with autistic disorder and to study their relationship with clinical characteristics.

Methods

We enrolled 22 adult patients with autistic disorder (mean age: 28.1 ± 7.7 years) and 28 age- and gender-matched healthy controls (mean age: 28.7 ± 8.1 years). Serum levels of HMGB1 were measured by enzyme-linked immunosorbent assay (ELISA).

Results

Compared with healthy subjects, serum levels of HMGB1 were significantly higher in patients with autistic disorder (10.8 ± 2.6 ng/mL versus 5.6 ± 2.5 ng/mL, respectively, P < 0.001). After adjustment for potential confounders, serum HMGB1 levels were independently associated with their domain A scores in the Autism Diagnostic Interview-Revised, which reflects their impairments in social interaction.

Conclusions

These results suggest that HMGB1 levels may be affected in autistic disorder. Increased HMGB1 may be a biological correlate of the impaired reciprocal social interactions in this neurodevelopmental disorder.