Konstantinos N. Fountoulakis

The International Society for Bipolar Disorders (ISBD) Task Force Report on Antidepressant Use in Bipolar Disorders

OBJECTIVE The risk-benefit profile of antidepressant medications in bipolar disorder is controversial. When conclusive evidence is lacking, expert consensus can guide treatment decisions. The International Society for Bipolar Disorders (ISBD) convened a task force to seek consensus recommendations on the use of antidepressants in bipolar disorders. METHOD An expert task force iteratively developed consensus through serial consensus-based revisions using the Delphi method. Initial survey items were based on systematic review of the literature. Subsequent surveys included new or reworded items and items that needed to be rerated. This process resulted in the final ISBD Task Force clinical recommendations on antidepressant use in bipolar disorder. RESULTS There is striking incongruity between the wide use of and the weak evidence base for the efficacy and safety of antidepressant drugs in bipolar disorder. Few well-designed, long-term trials of prophylactic benefits have been conducted, and there is insufficient evidence for treatment benefits with antidepressants combined with mood stabilizers. A major concern is the risk for mood switch to hypomania, mania, and mixed states. Integrating the evidence and the experience of the task force members, a consensus was reached on 12 statements on the use of antidepressants in bipolar disorder. CONCLUSIONS Because of limited data, the task force could not make broad statements endorsing antidepressant use but acknowledged that individual bipolar patients may benefit from antidepressants. Regarding safety, serotonin reuptake inhibitors and bupropion may have lower rates of manic switch than tricyclic and tetracyclic antidepressants and norepinephrine-serotonin reuptake inhibitors. The frequency and severity of antidepressant-associated mood elevations appear to be greater in bipolar I than bipolar II disorder. Hence, in bipolar I patients antidepressants should be prescribed only as an adjunct to mood-stabilizing medications.

Treatment of bipolar disorder: a systematic review of available data and clinical perspectives.

This paper is a systematic review of the available data concerning the treatment of bipolar disorder: a systematic Medline search concerning treatment guidelines and clinical trials. The search for treatment guidelines returned 583 articles and 913 papers for RCTs. The search was last performed on 1 March 2008. An additional search included repositories of clinical trials and previous systematic reviews in order to trace especially older trials. The literature suggests that lithium is useful during the acute manic and the maintenance phase. Both first- and second-generation antipsychotics are efficacious in the treatment of acute mania. Quetiapine and the olanzapine-fluoxetine combination are also effective for treating bipolar depression, while olanzapine, quetiapine and aripiprazole are effective during the maintenance phase. Anticonvulsants, particularly valproate and carbamazepine have antimanic properties, whereas lamotrigine may be preferably effective in the treatment of depression but not mania. Antidepressants should always be used in combination with an antimanic agent because they were reported to induce switching to mania or hypomania, mixed episodes, and rapid cycling when given as monotherapy. The best evidence-based psychosocial interventions for bipolar disorder are group- and family-focused psychoeducation. Electroconvulsive therapy is an option for refractory patients. Although a variety of treatment options for bipolar disorder is currently available, their effectiveness is far from satisfactory, especially against bipolar depression and maintenance. Combination therapy may improve treatment outcome but it also carries the burden of more side-effects. Further research as well as the development of better guidelines and algorithms for step-by-step rational treatment are necessary.

Association of the s allele of the 5-HTTLPR with neuroticism-related traits and temperaments in a psychiatrically healthy population

IntroductionResearch concerning the genetic background of traits, temperaments and psychiatric disorders has been rapidly expanding. One of the most frequently studied genetic polymorphisms in the background of psychological and psychiatric phenomena is the 5-HTTLPR polymorphism of the serotonin transporter gene which has earlier been found to be associated with neuroticism and neuroticism-related traits and disorders. However, both the neuroticism trait and psychiatric disorders are complex and composed of several subfacets. The aim of our study was to investigate the association of the 5-HTTLPR polymorphism with several smaller, distinct and better characterisable phenomena related to the neuroticism trait.Methods169 healthy females participated in the study. All participants completed the Buss–Durkee Hostility Inventory (BDHI), the State-Trait Anxiety Inventory (STAI), The Zung Self-rating Depression Scale (ZSDS), the Beck Hopelessness Scale, the SCL-51, the Temperament and Character Inventory (TCI) and the Temperament Evaluation of Memphis, Pisa, Paris and San Diego (TEMPS-A) questionnaire. All subjects were genotyped for the 5-HTTLPR using PCR. Data were analysed with ANOVA and MANCOVA with age as a covariate.ResultsWe found that the presence of the s allele was significantly associated with anxiety, depression, hopelessness, guilt, hostility, aggression, presence of neurotic symptoms, self-directedness and affective temperaments carrying a depressive component even when controlling for age.ConclusionsOur study is the first that confirms that traits and characteristics related to neuroticism, such as increased anxiety, depression, hopelessness, somatization, feeling of guilt, hostility, aggression, lack of self-directedness and affective temperament are consistently and independently associated with the 5-HTTLPR polymorphism of the serotonin transporter gene. Our study therefore suggests that neuroticism can be considered a unified construct not only from a phenotypical but also from a genetic point of view and 5HTTLPR can be considered one component of its polygenic background. Our results thus yield further insight into the role of the 5-HTTLPR in the background of neuroticism and neuroticism-related psychiatric disorders.

The validation of the short form of the Geriatric Depression Scale (GDS) in Greece

The Geriatric Depression Scale-15 (GDS-15) is a short, 15-item instrument specifically designed to assess depression in geriatric populations. Its items require a yes/no response. The Geriatric Depression Scale was first introduced by Yesavage et al. in 1983, and the short form (GDS-15) was developed by Sheikh and Yesavage in 1986. The aim of the current study was the standardization of the GDS-15 for use in Greece. Subjects were divided into Group A: 168 control subjects, and Group B: 103 patients suffering from clinically diagnosed depression. All were over 65 years of age. A score of 6/7 on the GDS-15 was found to be the best cut-off point for diagnosing depression in an elderly Greek population, with Sensitivity=92.23 and Specificity=95.24. GDS-15 manifests high internal consistency with Cronbach’s alpha=0.94, and all items seem to be equivalent. Factor Analysis of the GDS-15 revealed 4 factors: a cognitive (thought content), an affective, a functional, and a factor that reflects helplessness and fear for the future. The two diagnostic groups differed on all 4 factors scores at p-value <0.001.

Reliability, Validity and Psychometric Properties of the Greek Translation of the Center for Epidemiological Studies-Depression (CES-D) Scale

IntroductionThe aim of the current study was to assess the reliability, validity and psychometric properties of the Greek translation of the Center for Epidemiological Studies- Depression Scale (CES-D).Methods40 depressed patients 29.65 ± 9.38 years old, and 120 normal controls 27.23 ± 10.62 years old entered the study. In 20 of them (12 patients and 8 controls) the instrument was re-applied 1-2 days later. Translation and Back Translation was made. Clinical Diagnosis was reached by consensus of two examiners with the use of the SCAN v.2.0 and the IPDE. Statistical Analysis included ANOVA, the Pearson Product Moment Correlation Coefficient, Principal Components Analysis and Discriminant Function Analysis and the calculation of Cronbachs alpha (α)ResultsBoth Sensitivity and specificity exceed 90.00 at 23/24, Chronbachs alpha for the total scale was equal to 0.95. Factor analysis revealed three factors (positive affect, irritability and interpersonal relationships, depressed affect and somatic complains). The test-retest reliability was satisfactory (Pearsons R between 0.45 and 0.95 for individual items and 0.71 for total score).ConclusionThe Greek translation of the CES-D scale is both reliable and valid and is suitable for clinical and research use with satisfactory properties. Its properties are similar to those reported in the international literature. However one should always have in mind the limitations inherent in the use of self-report scales.

Efficacy of antidepressants: a re-analysis and re-interpretation of the Kirsch data

Recently there has been much debate on the true usefulness of antidepressant therapy especially after the publication of a meta-analysis by Kirsch et al. (PLoS Medicine 2008, 5, e45). The aim of the current paper was to recalculate and re-interpret the data of that study. Effect-size and mean-score changes were calculated for each agent separately as well as pooled effect sizes and mean changes on the basis of the data reported by Kirsch et al. The weighted mean improvement was (depending on the method of calculation) 10.04 or 10.16 points on the Hamilton Depression Rating Scale (HAMD) in the drug groups, instead of 9.60, and thus the correct drug-placebo difference is 2.18 or 2.68 instead of 1.80. Kirsch et al. failed to report that that the change in HAMD score was 3.15 or 3.47 points for venlafaxine and 3.12 or 3.22 for paroxetine, which are above the NICE threshold. Still the figures for fluoxetine and nefazodone are low. Thus it seems that the Kirsch et al.s meta-analysis suffered from important flaws in the calculations; reporting of the results was selective and conclusions unjustified and overemphasized. Overall the results suggest that although a large percentage of the placebo response is due to expectancy this is not true for the active drug and effects are not additive. The drug effect is always present and is unrelated to depression severity, while this is not true for placebo.

Reliability and psychometric properties of the Greek translation of the State-Trait Anxiety Inventory form Y: Preliminary data

BackgroundThe State-Trait Anxiety Inventory form Y is a brief self-rating scale for the assessment of state and trait anxiety. The aim of the current preliminary study was to assess the psychometric properties of its Greek translation.Materials and methods121 healthy volunteers 27.22 ± 10.61 years old, and 22 depressed patients 29.48 ± 9.28 years old entered the study. In 20 of them the instrument was re-applied 1–2 days later. Translation and Back Translation was made. The clinical diagnosis was reached with the SCAN v.2.0 and the IPDE. The Symptoms Rating Scale for Depression and Anxiety (SRSDA) and the EPQ were applied for cross-validation purposes. The Statistical Analysis included the Pearson Correlation Coefficient and the calculation of Cronbachs alpha.ResultsThe State score for healthy subjects was 34.30 ± 10.79 and the Trait score was 36.07 ± 10.47. The respected scores for the depressed patients were 56.22 ± 8.86 and 53.83 ± 10.87. Both State and Trait scores followed the normal distribution in control subjects. Cronbachs alpha was 0.93 for the State and 0.92 for the Trait subscale. The Pearson Correlation Coefficient between State and Trait subscales was 0.79. Both subscales correlated fairly with the anxiety subscale of the SRSDA. Test-retest reliability was excellent, with Pearson coefficient being between 0.75 and 0.98 for individual items and equal to 0.96 for State and 0.98 for Trait.ConclusionThe current study provided preliminary evidence concerning the reliability and the validity of the Greek translation of the STAI-form Y. Its properties are generally similar to those reported in the international literature, but further research is necessary.

Reliability, validity and psychometric properties of the Greek translation of the zung depression rating scale

IntroductionThe current study aimed to assess the reliability, validity and psychometric properties of the Greek translation of the Zung Depression Rating Scale (ZDRS).MethodsThe study sample included 40 depressed patients 29.65 ± 9.38 years old and 120 normal comparison subjects 27.23 ± 10.62 years old. In 20 of them (12 patients and 8 comparison subjects) the instrument was re-applied 1–2 days later. Translation and Back Translation was made. Clinical Diagnosis was reached by consensus of two examiners with the use of the SCAN v.2.0 and the IPDE. Statistical Analysis included ANOVA, the Pearson Product Moment Correlation Coefficient, Principal Components Analysis and Discriminant Function Analysis and the calculation of Cronbachs alpha (α)ResultsBoth Sensitivity and specificity exceed 90.00 at 44/45, Chronbachs alpha for the total scale was equal to 0.09, suggesting that the scale covers a broad spectrum of symptoms. Factor analysis revealed five factors (anxiety-depression, thought content, gastrenterological symptoms, irritability and social-interpersonal functioning). The test-retest reliability was satisfactory (Pearsons R between 0.92).ConclusionThe ZDRS-Greek translation is both reliable and valid and is suitable for clinical and research use with satisfactory properties. Its properties are similar to those reported in the international literature, although the literature is limited. However one should always have in mind the limitations inherent in the use of self-report scales.

Efficacy of pharmacotherapy in bipolar disorder: a report by the WPA section on pharmacopsychiatry

The current statement is a systematic review of the available data concerning the efficacy of medication treatment of bipolar disorder (BP). A systematic MEDLINE search was made concerning the treatment of BP (RCTs) with the names of treatment options as keywords. The search was updated on 10 March 2012. The literature suggests that lithium, first and second generation antipsychotics and valproate and carbamazepine are efficacious in the treatment of acute mania. Quetiapine and the olanzapine–fluoxetine combination are also efficacious for treating bipolar depression. Antidepressants should only be used in combination with an antimanic agent, because they can induce switching to mania/hypomania/mixed states/rapid cycling when utilized as monotherapy. Lithium, olanzapine, quetiapine and aripiprazole are efficacious during the maintenance phase. Lamotrigine is efficacious in the prevention of depression, and it remains to be clarified whether it is also efficacious for mania. There is some evidence on the efficacy of psychosocial interventions as an adjunctive treatment to medication. Electroconvulsive therapy is an option for refractory patients. In acute manic patients who are partial responders to lithium/valproate/carbamazepine, adding an antipsychotic is a reasonable choice. The combination with best data in acute bipolar depression is lithium plus lamotrigine. Patients stabilized on combination treatment might do worse if shifted to monotherapy during maintenance, and patients could benefit with add-on treatment with olanzapine, valproate, an antidepressant, or lamotrigine, depending on the index acute phase. A variety of treatment options for BP are available today, but still unmet needs are huge. Combination therapy may improve the treatment outcome but it also carries more side-effect burden. Further research is necessary as well as the development of better guidelines and algorithms for the step-by-step rational treatment.

Antidepressant medications and other treatments of depressive disorders: a CINP Task Force report based on a review of evidence

According to the World Health Organization, depression is one of the most debilitating disorders affecting humankind. The social and economic costs of chronic ill health resulting from untreated or inadequately treated depression are considerable and frequently underestimated. The CINP established the Task Force on Antidepressant Medications in 2004 to examine all aspects of therapy with antidepressant drugs. This was considered necessary as, despite the availability of effective antidepressants for the past 50 years, a substantial minority of depressed patients either remains untreated or under treated. As the only international organization devoted to the promotion of research, education and the applications of neuropsychopharmacology to the clinic, the main task of the CINP is to extend the knowledge of the drugs that are available with the aim of improving the management of mental disorders. The purpose of this Task Force document was not to produce an academic monograph nor a set of guidelines, but to provide mental health and other professionals with comprehensive and objective information about the different aspects of the use of antidepressants important in clinical practice. The Task Force consisted of 15 experts in psychiatry, psychopharmacology, public health, economics and family care. The majority of its members are senior members of the CINP. The Task Force was also advised to rely in the course of its work on advisors in different countries selected because of their outstanding expertise in the matters covered by the review. The report presented here was approved by the Executive Committee and the Council of the CINP at its meeting in Chicago in July 2006. As a service to those engaged in mental health care and to ensure maximum impact, the Task Force review is being published as a supplement to the CINPs journal, the International Journal of Neuropsychopharmacology. In addition, the information will later …