Psychometric properties of the 16-item Quick Inventory of Depressive Symptomatology: A systematic review and meta-analysis

Effective management of depression is predicated upon reliable assessment. The Quick Inventory of Depressive Symptomatology (QIDS) is a depression severity scale with both self-rated (QIDS-SR₁₆) and clinician-rated (QIDS-C₁₆) versions. Although widely used in research, the psychometric properties of the QIDS₁₆ have not been systematically reviewed. We performed a systematic review of studies of the psychometric properties (factor structure, internal consistency, convergent validity, discriminant validity, test-retest reliability and responsiveness to change) of the QIDS-SR₁₆ or QIDS-C₁₆. Six databases were searched: MEDLINE, EMBASE, PsycINFO, CinAHL, Web of Science and the Cochrane Central Register of Controlled Trials. Findings were summarised, bias assessed and correlations with reference standards were pooled. 37 studies (17,118 participants) were included in the review. Both versions of the QIDS₁₆ were unidimensional. Cronbach's alpha ranged from 0.69 to 0.89 for the QIDS-SR₁₆ and 0.65 to 0.87 for the QIDS-C₁₆. The QIDS-SR₁₆ correlated moderately to highly with several depression severity scales. Seven studies were pooled where QIDS-SR₁₆ was correlated with the HRSD-17 (r = 0.76, CI 0.69, 0.81) in patients diagnosed with depression. Four studies examined convergent validity with the QIDS-C₁₆. Four studies examined discriminant validity, for the QIDS-SR₁₆ alone. Eighteen studies had at least one author who was a co-author of the original QIDS₁₆ study. Most studies were conducted in the USA (n = 26). The QIDS-SR₁₆ and the QIDS-C₁₆ are unidimensional rating scales with acceptable internal consistency. To justify the use of the QIDS₁₆ scale in clinical practice, more research is needed on convergent and discriminant validity, and in populations outside the USA.     

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.     

Association between serotonin-related gene polymorphisms and suicidal behavior in depressive patients

BACKGROUND: Several studies have suggested that there is a substantial genetic contribution to suicidal behavior. Genes encoding proteins involved in serotonergic transmission are major candidates in association studies of suicidal behavior. In this study, we aimed to investigate the 5-HT2A receptor (5HTR2A) and tryptophan hydroxylase (TPH) genes for association with suicidal behavior in depressive patients. METHODS: Patients with major depression who had recently attempted suicide (n=191) and control subjects (n=193) were genotyped for 5HTR2A 102T/C, and TPH 218A/C. The lethality of the suicide attempt was measured using the Risk-Rescue Rating (RRR) and Lethality Suicide Attempt Rating Scale (LSARS). The severity of depression was measured using the Hamilton Depression Rating Scale (HDRS). RESULTS: There were no significant differences in the genotype distributions or allelic frequencies in the two serotonergic polymorphisms between suicide attempters and normal controls. None of the two serotonergic polymorphisms was correlated with lethality. CONCLUSIONS: We concluded that these polymorphisms may not be associated with susceptibility to suicidal behavior in our Korean population. Our results were in line with most previous studies. More work is needed to replicate these findings. Our future studies aim at identifying other genetic associations.     

Wolframin gene H611R polymorphism: No direct association with suicidal behavior but possible link to mood disorders

Wolframin gene polymorphisms, including the H611R polymorphism, are reportedly associated with mood disorders and psychiatric hospitalization, but there is disagreement about the association of this specific variant with suicidality and impulsive traits. This study tested the association of the H611R polymorphism with mood disorders, suicidal behavior, and aggressive–impulsive traits. Two hundred and one subjects with mood disorders and 113 healthy volunteers were genotyped for the H611R polymorphism and underwent structured interviews for diagnosis and clinical ratings. All were Caucasians. The H611R polymorphism was associated with mood disorders but not suicidal behavior, aggressive/impulsive traits or suicidality in first-degree relatives. The HR heterozygote genotype was more frequent in mood disorder (χ² = 7.505; df = 2; p = .023). If this finding will be replicated, the H611R polymorphism may be a possible marker for mood disorders in a psychiatric population, and not just in relatives of Wolfram syndrome probands.     

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.     

Sertraline treatment of patients with major depressive disorder who failed initial treatment with paroxetine or fluvoxamine

This study was undertaken to examine the long-term effectiveness and safety of switching to sertraline from other selective serotonin reuptake inhibitors (SSRIs) in the treatment of non-remitted or treatment-intolerant major depressive disorder. The study included 25 patients with major depressive disorder according to DSM-IV-TR criteria. None had achieved remission with paroxetine or fluvoxamine, but each had been used in an adequate dose for an adequate time period or had been intolerant of these SSRIs. Most patients (n=22, 88%) were non-remitters. Switching was accomplished by gradual cross-titration and tapering. We conducted assessments at baseline and at weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24. Outcomes were assessed using the Quick Inventory of Depressive Symptomatology-Self-Report, Japanese version (QIDS-SRJ) score (primary outcome), the 17-item Hamilton Depression Rating Scale (HDRS), and the Clinical Global Impressions (CGI) scale. Mean QIDS-SRJ and HDRS scores improved significantly from baseline to week 8 and week 24. At the respective endpoints of weeks 8 and 24, remitters on QIDS-SRJ (≤5) were 2 of 25 (8%) and 4 of 25 (16%). At weeks 8 and 24, 11 of 25 (44%) were responders on QIDS-SRJ (≥50% reduction). Five patients (20%) terminated early, before week 8, because of side effects and/or lack of efficacy. These preliminary data suggest that the switching strategy from paroxetine or fluvoxamine to sertraline might be effective and well-tolerated in patients with non-remitted or treatment-intolerant major depressive disorder.     

Role of serotonergic-related systems in suicidal behavior: Data from a case-control association study

Objective

To investigate whether functional polymorphisms directly (HTR2A and SLC6A4 genes) or indirectly (IL-1 gene complex, APOE and ACE genes) related with serotonergic neurotransmission were associated with suicidal behavior.

Subjects and methods

227 suicide attempters, 686 non-suicidal psychiatric patients, and 420 healthy controls from a homogeneous Spanish Caucasian population were genotyped using standard methods.

Results

There were no differences in genotype frequencies between the three groups. The −1438A/G [χ² (df) = 9.80 (2), uncorrected p = 0.007] and IL-1α −889C/T [χ² (df) = 8.76 (2), uncorrected p = 0.013] genotype frequencies between impulsive and planned suicide attempts trended toward being different (not significant after Bonferroni correction). Suicide attempts were more often impulsive in the presence of −1438G/G or IL-1α −889C/T or C/C genotypes. There was interaction between the polymorphism 5-HTTLPR and age [LRT (df) = 6.84 (2), p = 0.033] and between the polymorphisms APOE and IL-1RA (86 bp)_n [LRT (df) = 12.21 (4), p = 0.016] in relation to suicide attempt lethality.

Conclusion

These findings further evidence the complexity of the association between genetics and suicidal behavior, the need to study homogenous forms of the behavior and the relevance of impulsive and aggressive traits as endophenotypes for suicidal behavior.     

Source imaging of P300 auditory evoked potentials and clinical correlations in patients with posttraumatic stress disorder

Objective

Posttraumatic stress disorder (PTSD) is associated with abnormal information processing. The P300 component of event-related potentials (ERPs) is known to be a useful marker of information processing. The purposes of this study were to determine the P300 current source density in PTSD patients, and its relationship with symptom severity.

Methods

ERPs were recorded in 30 PTSD patients and 33 healthy controls while participants were performing the auditory oddball task. We compared P300 current source density data - obtained by standardized low-resolution brain electromagnetic tomography (sLORETA) - between the two groups. The correlation between P300 current source density and clinical symptoms (as evaluated using the Korean version of the Structured Interview for PTSD — K-SIPS and Davidson Trauma Scale — K-DTS) was conducted.

Results

In PTSD patients, the current source density of P300 is significantly reduced in the inferior frontal gyrus, precentral gyrus, insula, and anterior cingulate compared to healthy controls. Total K-DTS scores were correlated with the P300 current source density in the posterior cingulate gyrus. The K-SIP B items (re-experiencing) and K-SIB D items (increased arousal) were positively correlated with P300 current source densities in several brain regions located in the frontal, parietal, and temporal lobe (p < 0.05). Conversely, the K-SIP C items (avoidance and numbing) were negatively correlated with P300 current source densities in the superior and middle frontal gyri in the frontal lobes (p < 0.05).

Conclusion

The P300 current source densities reflected the pathophysiology of PTSD patients. PTSD symptoms were related to different neural activities, depending on their symptom characteristics.     

Review of major measuring instruments in comorbid depression and coronary heart disease

Depression and coronary heart disease (CHD) are common comorbid conditions in which each may be a risk factor for the other condition. However, treating depression does not appear to favorably alter cardiac outcome when depression and CHD are comorbid. The National Heart Lung and Blood Institute working group convened in August, 2004 reviewed and recommended instruments to assess and treat depression in subjects with CHD. This paper focuses on these instruments and their limitations when compared and contrasted with the robust instruments available to assess CHD.As a result of our observations about the limitations of instruments and scales available to assess depression and depressive symptoms in subjects with comorbid CHD, we propose using the objectivity of CHD parameters to assess the efficacy of psychiatric interventions in patients with comorbid depression and to better define the link between depression and these cardiac conditions.     

The ALDH2 and 5-HT2A genes interacted in bipolar-I but not bipolar-II disorder

Objective

Clarifying the similarities and differences between the two most common subtypes of bipolar disorder, bipolar-I and bipolar-II, is essential for improving our understanding of them. Because the serotonergic system has been implicated in the pathogenesis of bipolar disorder, it may be important to investigate genes such as the aldehyde dehydrogenase 2 (ALDH2) and serotonin 2A receptor genes, which are involved in metabolizing serotonin and encoding serotonin receptors. We examined the association of the ALDH2 and 5-HT2A-A1438G polymorphisms with bipolar I and II and possible interactions between these genes.

Methods

One thousand forty-nine participants were recruited: 249 with bipolar-I, 456 with bipolar-II, and 344 healthy controls. The genotypes of the ALDH2 and 5HT2A-A1438G polymorphisms were determined using polymerase chain reactions plus restriction fragment length polymorphism analysis.

Results

Logistic regression analysis showed a significant effect of the ALDH2 and the 5-HT2A-A1438G polymorphisms, and a significant interaction effect for the A/G genotypes of the 5-HT2A-A1438G polymorphism and the ALDH2*1*1 genotypes (p = 0.004) discriminated between bipolar-I patients and controls without bipolar disorder. These polymorphisms, however, were not associated with bipolar-II disorder.

Limitations

The significant differences of age and gender between patients and controls limit the comparison, although statistical adjustments were made for them.

Conclusion

Our findings provide initial evidence that the ALDH2 and 5-HT2A genes interact in bipolar-I but not in bipolar-II disorder. Our findings suggest a unique genetic distinction between bipolar-I and bipolar-II.     

Impaired MMN/P3a complex in first-episode psychosis: Cognitive and psychosocial associations

Mismatch negativity (MMN) is a neurophysiological indicator of the brain's ability to extract relevant information from an irrelevant background. The P3a orienting response often accompanies MMN in deviance detection paradigms. Both MMN and P3a have been described as reliable biomarkers of schizophrenia. MMN/P3a impairments are associated with deficits in verbal memory and attentional switching, reflecting dysfunctions in the temporal and frontal systems, respectively. It remains unresolved whether MMN/P3a are robust biomarkers of psychosis in first-episode patients. Thirty-four young people (18 to 30 years) were assessed in this study; 17 first-episode psychosis (FEP) patients were compared to 17 healthy controls. To elicit MMN/P3a, a two-tone passive auditory oddball paradigm with 8% duration deviants was used; event-related potentials were recorded at frontal, central and temporal (mastoid) sites. Neuropsychological assessments included processing speed, attentional switching, simple attention, and verbal learning and memory. Social functioning and quality of life measures were also obtained. The FEP group showed significantly reduced MMN amplitudes compared to controls. The FEP group also showed significantly reduced P3a amplitudes at frontal and central sites compared with controls. As expected, the FEP group also showed significant deficits in attention and verbal learning/memory. Correlational analyses found strong associations between fronto-central MMN/P3a peak amplitude and cognitive/psychosocial functioning. This study provides evidence of early neurobiological markers in young people with FEP. These findings suggest that MMN/P3a impairments are present at early stages of psychosis and that fundamental pre-attentive/deviance detection deficits may mark the beginning of progressive underlying changes with illness onset. Such deficits in FEP appear to have important links with higher-order cognitive and psychosocial functioning.     

Lithium addition in antidepressant-resistant depression: effects on platelet 5-HT, plasma 5-HT and plasma 5-HIAA concentration

The efficacy of the addition of lithium to an established course of antidepressant treatment can be explained by a synergistic effect of the two drugs on central 5-HT neurotransmission. In the present study we investigated the effect of lithium addition on the 5-HT concentration in plasma and platelets and the concentration of 5-HIAA. Thirty-nine depressed inpatients who fulfilled the DSM-IV criteria for major depressive disorder and who did not respond to monotherapy with either imipramine or fluvoxamine participated in this study. Concentration of 5-HT in both plasma and platelets did not change significantly during lithium addition. The 5-HT ratio (plasma concentration/platelet concentration) shows a small non-significant increase after 3 weeks lithium addition. The mean concentration of 5-HIAA shows a significant increase during lithium addition; with no difference between the imipramine and the fluvoxamine sample. The increments in 5-HIAA concentration during lithium addition are indicative of an increased 5-HT turnover.     

Association of the STin2 polymorphism of the serotonin transporter gene with a neurocognitive endophenotype in major depressive disorder

BACKGROUND:: The aim of our study was to investigate the association of STin2 polymorphism and cognitive dysfunction in major depression. METHODS:: 71 patients with major depression and 99 controls were genotyped for STin2. All depressive subjects and 30 controls also completed tests measuring neurocognitive performance. RESULTS:: We found a significantly higher frequency of the STin2.10/Stin2.10 homozygous genotype in the depressed group compared to controls. In the depressed group subjects with at least one copy of the 10-repeat allele showed decreased interference threshold in Stroop III compared to patients without the 10-repeat allele. Average performance of the depressed group without the 12-repeat allele was significantly weaker in the Rey Auditory Verbal Learning Test working memory and recall tasks compared to patients having at least one copy of the 12-repeat allele. CONCLUSION:: Our results suggest that the presence of STin2.10 and absence of STin2.12 allele may be related to a possible genetic endophenotype for characteristic cognitive dysfunctions detected in MDD.     

Serotonin system gene polymorphisms are associated with impulsivity in a context dependent manner

Impulsivity is a risk factor for adverse outcomes and characterizes several psychiatric disorders and risk for suicide. There is strong evidence that genetic variation influences individual differences in impulsivity, but the details are not yet understood. There is growing interest in better understanding the context dependency of genetic effects that is reflected in studies examining gender specificity, gene×environment interaction and epistasis (gene-gene interaction). In a cross-sectional study we examined whether polymorphisms in six serotonin system candidate genes and the experience of early life trauma (age 0-12) were associated with individual differences in impulsivity in a non-clinical sample of Caucasian university students (N=424). We specifically tested potential gender specific, gene-gene, and gene×environment (early life trauma) effects. In our main analyses with Barratt Impulsiveness Scale (BIS-11) total score, there were significant (i.e. p<.01 and False Discovery Rate <.10) interactions between (1) gender and TPH2 (rs1386483) genotype; (2) gender and HTR2A (rs6313) genotype; and epistatic interactions among (3) 5-HTTLPR and MAOA uVNTR; (4) 5-HTTLPR and rs6313 and (5) HTR1B (rs6296) and rs6313 genotypes. Our results strongly support the explicit investigation of context dependent genetic effects on impulsivity and may help to resolve some of the conflicting reports in the literature.     

Comparison of petal of Crocus sativus L. and fluoxetine in the treatment of depressed outpatients: a pilot double-blind randomized trial

Depression is one of the most common neuropsychiatric conditions, with a lifetime prevalence approaching 17%. Although a variety of pharmaceutical agents is available for the treatment of depression, psychiatrists find that many patients cannot tolerate the side effects, do not respond adequately, or finally lose their response. On the other hand, many herbs with psychotropic effects have far fewer side effects. They can provide an alternative treatment or be used to enhance the effect of conventional antidepressants. A number of recent preclinical and clinical studies indicate that stigma and petal of Crocus sativus have antidepressant effect. Our objective was to compare the efficacy of petal of C. sativus with fluoxetine in the treatment of depressed outpatients in an 8-week pilot double-blind randomized trial. Forty adult outpatients who met the DSM- IV criteria for major depression based on the structured clinical interview for DSM- IV participated in the trial. Patients have a baseline Hamilton Rating Scale for Depression score of at least 18. In this double-blind and randomized trial, patients were randomly assigned to receive capsule of petal of C. sativus 15 mg bid (morning and evening) (Group 1) and fluoxetine 10 mg bid (morning and evening) (Group 2) for a 8-week study. At the end of trial, petal of C. sativus was found to be effective similar to fluoxetine in the treatment of mild to moderate depression (F=0.03, d.f.=1, P=0.84). In addition, in the both treatments, the remission rate was 25%. There were no significant differences in the two groups in terms of observed side effects. The present study is supportive of other studies which show antidepressant effect of C. sativus.     

Fluoxetine versus sertraline in the treatment of patients with undifferentiated somatoform disorder: a randomized, open-label, 12-week, parallel-group trial

The present study was conducted to compare the effectiveness and tolerability of fluoxetine and sertraline in the treatment of undifferentiated somatoform disorder (USD), using the Patient Health Questionnaire (PHQ-15), which was specifically designed for assessing the severity of somatic symptoms. A randomized, 12-week, open-label trial of fluoxetine (10-60 mg/d) and sertraline (25-350 mg/d) in patients with USD was conducted. Six visits, at baseline and weeks 1, 2, 4, 8, and 12, were scheduled. Assessments for effectiveness and tolerability were conducted at each visit. The primary effectiveness measure was the mean change in PHQ-15 total score, from baseline to the end of treatment. Secondary effectiveness measures were the mean changes in total scores on the Beck Depression Inventory (BDI) and the 12-item General Health Questionnaire (GHQ-12), from baseline to the end of treatment. A total of 45 subjects were enrolled; of them, 28 were randomly assigned to receive fluoxetine and 17 to receive sertraline. The total score on the PHQ-15 from baseline to the end of treatment significantly decreased in the fluoxetine (-10.7, p<0.0001) and sertraline (-10.3, p<0.0001) treatment groups, with no between-group difference (F=0.0701, p=0.7924). Overall, both treatments were well tolerated and no serious adverse event was reported. This study suggests that both agents may have a potential role in the treatment of USD. A double-blind, placebo-controlled trial and/or head-to-head comparison study with larger samples are required to draw more definite conclusions.     

Combination therapy with amisulpride and antidepressants: clinical observations in case series of elderly patients with psychotic depression

Psychotic depression is classified as a clinical subtype of major depressive disorder. The combination of an antidepressant with an antipsychotic agent has been demonstrated to be efficacious for the treatment of psychotic depression. However, in elderly patients with psychotic depression, little information is available on the efficacy of such combinations. Therefore, we have evaluated combination treatment for 5 weeks with amisulpride and antidepressants in non-demented elderly patients with psychotic depression. Eleven patients were treated with either citalopram 20-40 mg/day (n=5) or mirtazapine 30-60 mg/day (n=6), and amisulpride 75-100 mg/day for 5 weeks. Clinical status was evaluated at baseline and after 3 and 5 weeks using the Brief Psychiatric Rating Scale (BPRS), the Hamilton Depression Rating Scale--17 items (HDRS) and the Clinical Global Impression Scale (CGI-S). In 5 of the 11 patients there was remission of depression, while in another 5 patients there was partial remission of depression and in one patient there was no remission. Finally, there was resolution of psychotic symptoms in all the patients involved. One patient developed tremor and rigidity but insisted on continuing with the drug since her psychopathology has improved considerably after the addition of amisulpride to antidepressant treatment. In conclusion, some of the elderly patients with psychotic depression may benefit from the combination of amisulpride and antidepressant pharmacotherapy.     

Fish oil supplementation in the treatment of major depression: a randomised double-blind placebo-controlled trial

Dietary deficiencies in essential omega-3 polyunsaturated fatty acids derived from fish are associated with depression and some fish oils may have therapeutic benefits. We aimed to determine whether taking tuna fish oil confers any additional benefit to conventional outpatient treatment for major depression. A randomized double-blind placebo-controlled four-month trial comparing tuna fish oil versus placebo was conducted on 83 outpatients with major depression. Despite large reductions in depression there were no significant differences at any assessment time point between patients receiving fish oil compared to placebo. Red blood cell incorporation of fatty acids indicated good compliance with oil supplementation, although this sample was not initially deficient in omega-3s. This particular dose and type of fish oil conferred no additional benefit to conventional treatment of depression in this sample. Future studies could target participants with pre-existing omega-3 deficiency and appraise alternate enriched types and higher doses of omega-3 supplementation.