Biomedical subjects

Mazda Adli

Publications and source records attributed to Mazda Adli.

14 recordsLinked to original sources

PubMed2025

Polygenic Contributions to Lithium Augmentation Outcomes in Unipolar Depression.

IMPORTANCE: Lithium augmentation is an effective treatment for patients with major depression after inadequate antidepressant response, but therapeutic outcomes vary considerably between individuals. Molecular studies may provide novel insights into treatment prediction and guide personalized therapy. OBJECTIVE: To investigate the association of polygenic risk scores (PRS) for schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) with clinical outcomes after lithium augmentation. DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed prospectively assessed treatment outcomes in patients who underwent lithium augmentation. Disorder-specific PRS were calculated using well-powered genome-wide association study summary statistics. Participants were recruited from 13 psychiatric hospitals, primarily in the greater Berlin area, between 2008 and 2020. They were patients with MDD who showed inadequate response to at least 1 antidepressant, a baseline score of 12 or more on the 17-item Hamilton Depression Rating Scale (HAMD-17), adequate treatment duration (≥4 weeks), and no diagnostic or co-medication changes. Data analysis was conducted between June 2022 and November 2023. EXPOSURE: Polygenic risk scores for MDD, SCZ, or BIP. MAIN OUTCOMES AND MEASURES: Response was defined as a 50% or greater reduction in HAMD-17 score, remission as a HAMD-17 score of 7 or less. Cox proportional hazards models, adjusted for ancestry, demographic, and clinical covariates, were used to estimate hazard ratios (HRs) for favorable outcomes. RESULTS: Among 193 patients (mean [SD] age, 49.5 [13.4] years; 118 [61.1%] female and 75 [38.9%] male), higher BIP-PRS were associated with both response (HR, 1.29; 95% CI, 1.02-1.63; P = .03) and remission (HR, 1.52; 95% CI, 1.14-2.04; P = .004), explaining 2.51% and 4.53% of the variability in treatment outcomes, respectively. Individuals in the highest tertile of the BIP-PRS distribution had a 2.02-fold (95% CI, 1.15-3.53) higher likelihood of response and a 2.26-fold (95% CI, 1.17-4.36) higher chance of remission compared with those in the lowest tertile. Additionally, lower MDD-PRS was associated with better response to lithium augmentation (HR, 0.81; 95% CI, 0.66-1.00; P = .048; Nagelkerke R2 = 1.99%). No significant associations were observed between SCZ-PRS and response (HR, 1.00; 95% CI, 0.80-1.24; P = .97) or remission (HR, 1.12; 95% CI, 0.85-1.48; P = .42). CONCLUSIONS AND RELEVANCE: Individuals carrying a higher polygenic burden for BIP and lower polygenic risk for MDD are more likely to benefit from lithium augmentation. Our findings suggest that disease-related PRS may aid in developing treatment prediction models for lithium augmentation response in depression, potentially informing clinical decision-making.

Humans↗

PubMed2006

Algorithms and collaborative-care systems for depression: are they effective and why? A systematic review.

BACKGROUND: Treatment algorithms and collaborative-care systems are systematic treatment approaches that are designed to improve outcomes by enhancing the quality of care. During the last decade, algorithm research has evolved as a new branch of clinical research that evaluates the clinical and economic impact of algorithm-guided treatment in primary and psychiatric care of patients with depressive disorders. METHODS: This article discusses the rationale of algorithm development, their risks and limitations, and important elements in their implementation in clinical practice. It further reviews the available studies that have evaluated algorithm-guided treatment for depression. RESULTS: Recent studies show that compared with treatment as usual, the use of algorithms and collaborative-care approaches in the care of depressed patients enhances treatment outcomes by modifying practice procedures and treatment processes. CONCLUSIONS: Treatment algorithms and collaborative-care systems clearly increase the efficacy of applied treatments in the care of depressed patients. However, to what extent the enhanced outcomes are a result of diligent measurement-based care or of the specific treatment steps that are used remains to be resolved. Valid clinical or pharmacogenetic predictors of response are needed to further tailor specific algorithms to individual patients.

Algorithms↗

PubMed2005

Is dose escalation of antidepressants a rational strategy after a medium-dose treatment has failed? A systematic review.

BACKGROUND: Maximizing the dose of antidepressants is widely recommended in cases of non-response to medium-dose treatment. However, scientific evidence supporting high-dose treatment is scarce. Systematic studies comparing dose escalation with alternative strategies for refractory depression (i. e. augmentation or change of compound) are lacking. The aim of this publication is to review available direct and indirect evidence concerning dose increase of antidepressants after a medium-dose trial has failed. METHOD: We performed a systematic literature search of Medline (1966-2003) and reviewed studies and publication references for available evidence. DATA SOURCES AND STUDY SELECTION: Studies of the following types were included: 1) dose increase studies in treatment refractory patients, 2) comparative dose studies, 3) therapeutic drug monitoring studies. RESULTS: Available data suggest differential efficacy of various pharmacological classes at more than medium-dosage. Direct evidence shows no increase of efficacy with high-dose selective serotonin reuptake inhibitor (SSRI) treatment; however, indirect evidence suggests enhanced therapeutic efficacy with high-dose tricyclic antidepressants. Few clinical data show ultra-high-dose treatment with the irreversible monoamine-oxidase-(MAO-) inhibitor tranylcypromine to be effective for refractory depression. Data concerning other selective compounds are insufficient to allow any definitive conclusion on the benefit of high-dose treatment. CONCLUSIONS: Based on available data highdose antidepressant treatment of patients refractory to medium-dose treatment is recommended for tricyclic compounds but not for SSRI. Some data suggest beneficial efficacy of ultra-high doses of the irreversible MAOI tranylcypromine. Research on other substance groups is limited and inconclusive. Prospective studies comparing dose escalation with alternative strategies for treatment of non-responding patients are needed.

Antidepressive Agents↗

PubMed2005

Long-term combination therapy versus monotherapy with lithium and carbamazepine in 46 bipolar I patients.

BACKGROUND: Despite wide clinical use of mood-stabilizer combinations for long-term treatment of patients with bipolar disorder, research on risks and benefits of this practice is limited. We found 14 small, usually brief, clinical trials of maintenance treatment with lithium plus carbamazepine. These trials suggest added benefit of combination treatment over use of either agent alone but also indicate the need for further studies. METHOD: In a post hoc analysis, we reviewed the course of 46 patients with DSM-IV-diagnosed bipolar I disorder identified as not improving during long-term monotherapy in a mood disorders clinic, comparing days per year hospitalized in 3 consecutive time periods: before prophylactic treatment, during monotherapy with lithium (N = 31) or carbamazepine (N = 15), and during their combined use (N = 46). Secondary outcome measures were rates of hospitalization, time to first recurrence of an affective episode, use of adjunctive treatments, and adverse effects. We compared outcomes with nonparametric bivariate methods and tested predictive factors by multiple regression. RESULTS: Subjects showed significant reductions in hospitalized days per year during combination therapy, averaging a decrease of 55.9% (p = .004). Among secondary outcomes, hospitalizations per year fell by 36.1%, and median time to recurrence nearly doubled during combination therapy. Rates of adverse effects increased 2.5-fold, compared with monotherapy, and use of adjunctive psychotropic agents increased by 21.9%. CONCLUSION: Combining lithium with carbamazepine yielded substantial benefit but more adverse effects.

Adult↗

PubMed2005

Long-term lithium treatment and thyroid antibodies: a controlled study.

OBJECTIVE: Because the role of thyroid autoimmunity in the development of lithium-induced thyroid dysfunction remains controversial, we compared the prevalence of thyroid autoantibodies in patients with affective disorders receiving long-term lithium maintenance therapy with that of age- and sex-matched controls. METHODS: We conducted a cross-sectional study with 100 adult patients with major affective disorders diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, revised (DSM-III-R), who were undergoing lithium therapy for 6 months or more at a specialized lithium university clinic and 100 age- and sex-matched controls with no history of an axis I psychiatric disorder. Serum autoantibodies against thyroid peroxidase (TPOAb), thyroglobulin (TgAb) and TSH receptors (TRAb) were measured. RESULTS: TPOAb were found in 7 patients and 11 controls, and TgAb were found in 8 patients and 15 controls. TRAb were not found in either group. CONCLUSIONS: In this sample of patients with affective disorders, long-term lithium treatment did not increase the prevalence of thyroid autoimmunity.

Adult↗

PubMed2003

Lithium augmentation increases post-dexamethasone cortisol in the dexamethasone suppression test in unipolar major depression.

Although considerable evidence exists on the efficacy of lithium as an augmenting agent in refractory depression, the underlying neurobiology of this phenomenon is unknown. In patients with major depression, changes of the hypothalamic-pituitary-adrenocortical (HPA) system have been detected by means of the dexamethasone suppression test (DST), when administered during treatment with tricyclic antidepressants. We investigated whether the DST also reveals alterations of the HPA system during lithium augmentation. We also sought to identify whether response to lithium augmentation can be predicted with the DST. Twenty-five patients with unipolar major depression, who did not respond to an adequate antidepressant monotherapy of at least 4 weeks, were measured for basal (pre-dexamethasone, 0800h) cortisol and ACTH levels and were administered the DST the day before initiation of lithium augmentation treatment. The same neuroendocrine procedures were repeated after 3 to 4 weeks. Criteria of response to lithium augmentation, defined as a reduction of the Hamilton Depression Rating Scale (HDRS17) score by > or =50% and an end point score of 9 or less, were determined by weekly HDRS ratings. The DST revealed a statistically significant increase of the post-dexamethasone cortisol values (P = 0.021) and an increase in the post-dexamethasone ACTH values (P = 0.051) during lithium augmentation as compared to pre-treatment baseline evaluations. The pre-dexamethasone hormone values were unchanged. The number of non-suppressors at baseline was one and increased to three at follow-up. Results of DST did not predict response to lithium augmentation, which occurred in 40% of subjects. Results suggest that lithium augmentation increases HPA system activity, as indicated by the increase of post-dexamethasone cortisol and ACTH levels measured by the DST. This is in contrast to the established decline of HPA system activity during treatment with tricyclic antidepressants.

Adolescent↗

PubMed2003

Lithium augmentation therapy in refractory depression-update 2002.

Lithium has been used to augment the efficacy of antidepressant medications for more than 20 years. The present study examines whether evidence exists to support the clinical efficacy of lithium augmentation in refractory, treatment resistant depression. Studies were identified by searching Medline (1980 to August 2002) and by scanning the references of published reviews and standard textbooks. Studies were selected if they were open-labeled or double-blind, placebo-controlled or comparator trials that involved patients who had not responded to conventional antidepressants. 27 prospective studies were identified that included a total of 803 depressed patients displaying the following designs: 10 double-blind, placebo-controlled trials, 2 randomized, double-blind comparator trials, 2 randomized, open comparator trials, and 13 open-label trials. The majority of randomized controlled trials has demonstrated substantial efficacy of lithium augmentation in partial and non responders to antidepressant treatment. In the placebo-controlled trials, the response rate in the lithium group was 45% and in the placebo group 18% (p<0.001). Summarizing all open and controlled studies, approximately 50% of patients responded to lithium augmentation within 4 weeks. In conclusion, lithium is the foremost and most well-documented augmentation strategy in refractory depression.Therefore, it should be considered a first-line treatment strategy in patients with major depression who do not adequately respond to standard antidepressants.

Adult↗

PubMed2003

Lithium augmentation therapy in refractory depression: clinical evidence and neurobiological mechanisms.

OBJECTIVE: This systematic review examines the evidence and discusses the clinical relevance of lithium augmentation as a treatment strategy for refractory major depressive episodes. It also examines hypotheses on the mode of action of lithium augmentation, with a focus on serotonin (5-HT) and neuroendocrine systems, and proposes recommendations for future research. METHOD: We searched the Medline computer database and the Cochrane Library for relevant original studies published in English from January 1966 to February 2003. The key words were as follows: lithium, augmentation strategies, lithium augmentation, major depression, refractory depression, treatment-resistant depression, neuroendocrinology, and serotonin. RESULTS: Of 27 prospective clinical studies published since 1981, 10 were double-blind, placebo-controlled trials, 4 were randomized comparator trials, and 13 were open-label trials. Five of 9 acute-phase placebo-controlled trials demonstrated that lithium augmentation had substantial efficacy. In the acute-treatment trials, the average response rate in the lithium group was 45%, and in the placebo group, 18% (P < 0.001). One placebo-controlled trial showed the efficacy of lithium augmentation in the continuation-phase treatment. Summarizing the open and controlled data, approximately 50% of patients responded to lithium augmentation within 2 to 6 weeks. Animal studies offer robust evidence that lithium augmentation increases 5-HT neurotransmission, possibly by a synergistic action of lithium and the antidepressant on brain 5-HT pathways. CONCLUSIONS: Augmentation of antidepressants with lithium is the best-documented augmentation therapy in the treatment of refractory depression. Emerging data from animal studies suggest that the 5-HTergic system is involved in the augmentatory effect of lithium.

Animals↗

PubMed2003

Hypothalamic-pituitary-thyroid system activity during lithium augmentation therapy in patients with unipolar major depression.

OBJECTIVE: Lithium augmentation is an established strategy in the treatment of refractory depression, but little is known about predictors of response and its mode of action. There is increasing evidence that low thyroid function indices within the normal range are associated with a poorer treatment response to antidepressants, but previous studies on the hypothalamic-pituitary-thyroid (HPT) system during lithium augmentation provide inconclusive results and have methodological limitations. This study aimed at exploring the role of thyroid function in lithium augmentation and used a prospective design that included a homogeneous sample of inpatients with unipolar major depressive disorder. METHODS: In 24 euthyroid patients with a major depressive episode who had not responded to antidepressant monotherapy of at least 4 weeks, we measured serum thyroid-stimulating hormone (TSH), total triiodothyronine (T3) and total thyroxine (T4) before (baseline) and during lithium augmentation therapy (follow-up). The time point of the endocrinological follow-up depended on the status of response, which was assessed weekly with the Hamilton Depression Rating Scale, 17-item version (HDRS17). Responders were reassessed immediately after response was determined, and non-responders after 4 weeks of lithium augmentation. RESULTS: There was a statistically significant change in thyroid system activity during lithium augmentation, with an increase of TSH levels and a decrease of peripheral T3 and T4 levels. However, there were no differences in any of the HPT hormones between responders and non-responders at baseline or at follow-up. CONCLUSIONS: The decrease of thyroid system activity during lithium treatment reflects the well-established "antithyroid" properties of lithium. However, it appears that thyroid status does not predict response to lithium augmentation in euthyroid patients before treatment.

Adult↗

PubMed2002

Supraphysiological doses of L-thyroxine in the maintenance treatment of prophylaxis-resistant affective disorders.

This prospective open-label study examined the efficacy of adjunctive supraphysiological doses of L-thyroxine (T(4)) in the maintenance treatment of prophylaxis-resistant affective disorder. Twenty-one (16 women, 5 men) of 25 patients enrolled consecutively over an 8-year period on the basis of their status of prophylaxis resistance (defined as two or more failures to standard prophylactic trials) participated for more than four months in the study and were eligible for the intention-to-treat analysis. The mean length of adjunctive treatment with T(4) was 51.4 +/- 21.7 months. The mean T(4) dose at study end was 378.6 +/- 90.2 micro g/d. The number of episodes and hospitalizations, and the morbidity indices during the time of prophylactic T(4) treatment, were compared with those measured for the same length of time before the start of T(4) treatment (mirror-image method). On the Clinical Global Impression for Bipolar Disorder scale (CGI-BP, Change from Worst Phase of Illness), eleven subjects (52.4%) were rated as "very much improved", four (19%) as "much improved", two (9.5%) as "minimally improved" and four (19%) as "no change." The mean total number of recurrences (8.6 before T(4) treatment vs. 2.8 during T(4) treatment; p =.004), the number of hospitalizations (3.1 vs. 1.9; p =.026) and the Morbidity Index (MI(Total) = 0.71 vs. MI(Total) = 0.28; p <.001) significantly declined during T(4) treatment. Subjects with bipolar disorder (n = 13) benefited more from the T4 treatment intervention than did subjects with unipolar major depressive disorder (n = 4) and schizoaffective disorder (n = 4). In conclusion, adjunctive treatment with L-thyroxine in supraphysiological doses may be an effective strategy in the maintenance treatment of patients with prophylaxis-resistant affective disorders.

Adult↗

PubMed2002

Lithium augmentation increases the ACTH and cortisol response in the combined DEX/CRH test in unipolar major depression.

Lithium augmentation is a well established strategy for treatment-resistant depression. The exact mode of its action is unknown, but an enhancement of serotonergic transmission is hypothesized. The authors investigated changes in the hypothalamic-pituitary-adrenocortical (HPA) system during lithium augmentation and their correlation to clinical response by means of the combined dexamethasone/CRH test (DEX/CRH test). Thirty patients with unipolar major depressive episodes (DSM IV) who had not responded to an adequate trial with an antidepressant were assessed on the day before lithium augmentation (baseline) with the DEX/CRH test (pretreatment with 1.5 mg dexamethasone p.o. at 11 P.M. and CRH stimulation at 3 P.M. on the next day). Twenty-four patients were re-assessed after response was determined or, in cases of non-response, four weeks after initiation of lithium augmentation. Response to lithium augmentation was measured by weekly ratings on the Hamilton Depression Rating Scale (HDRS 17-item version). Response was defined as a DeltaHDRS of > or =50% and an endpoint score of < 10. Patients had a significantly higher ACTH and cortisol response to CRH stimulation during lithium augmentation compared with the values at baseline. There was no difference in ACTH and cortisol reaction between responders and non-responders to lithium augmentation. This increase is in contrast to the known normalization of HPA-axis overdrive after treatment with a tricyclic antidepressant like amitriptyline. Because the effect was independent of response status we suggest that this increase reflects an effect of lithium that is independent from the psychopathological state or its change. This effect might be explained by the serotonergic effects of lithium.

Adolescent↗

PubMed2002

How long should the lithium augmentation strategy be maintained? A 1-year follow-up of a placebo-controlled study in unipolar refractory major depression.

There is compelling evidence from placebo-controlled studies that lithium augmentation is an effective strategy in the acute and continuation treatment of refractory unipolar major depression. Authors prospectively investigated the 1-year outcome of 22 subjects diagnosed with unipolar major depression who had participated in a 4-month placebo-controlled, double-blind continuation study of lithium augmentation without relapse. At the end of the double-blind phase, the blinded medication (lithium in 14 patients, placebo in 8 patients) was tapered off over a 1-week period, while the antidepressant was continued at the same dosage for another 4 weeks. Subsequently, the antidepressant was gradually discontinued over a 4-week period. Clinical status was assessed at regular follow-up visits. During the open 6-month follow-up period, seven subjects suffered an affective recurrence, five of whom had received lithium during the placebo-controlled, double-blind phase of the study. Study data suggest that active medication should be maintained for at least 1 year after successful lithium augmentation in patients with unipolar major depressive disorder.

Adult↗

PubMed2002

Effectiveness and feasibility of a standardized stepwise drug treatment regimen algorithm for inpatients with depressive disorders: results of a 2-year observational algorithm study.

BACKGROUND: The goal of the Berlin Algorithm Project is to establish a standardized stepwise drug treatment regimen (SSTR) for the treatment of inpatients with depressive disorders. We are reporting on the first of 3 subsequent study phases evaluating effectiveness and feasibility of the SSTR in a naturalistic clinical setting. METHOD: Patients with depressive disorders (International Classification of Diseases, Ninth Revision criteria) admitted to an academic medical center for inpatient treatment were enrolled in the SSTR protocol that comprised an algorithm-guided sequential treatment process (including pharmacologic washout period, sleep deprivation, antidepressant monotherapy, lithium augmentation, monoamine oxidase inhibitor treatment, and electroconvulsive therapy) dependent on the scores of a standardized assessment of treatment outcome, the Bech Rafaelsen Melancholia Scale (BRMS). RESULTS: Of 248 patients with depression, 119 (48%) were enrolled in the SSTR protocol. One hundred twenty-nine patients (52%) were not included, mostly due to individualized treatment procedures. An intent-to-treat (ITT) analysis showed that 38% of enrolled patients achieved remission (BRMS score < or = 5), 34% achieved "classic" response (deltaBRMS score > or = 50%), 15% achieved "low" response (deltaBRMS score 26% to 49%), and 13% did not respond. The overall response rate (remitters and classic responders) of SSTR treatment was 72% of the ITT sample. Twenty-one patients (18%) dropped out from the SSTR as nonresponders and 19 patients (16%) dropped out as low responders due to protocol deviations. CONCLUSION: The acceptance of the antidepressive treatment algorithm among physicians not specifically trained was moderate, resulting in a relatively low enrollment rate. However, once patients were enrolled into the study, adherence to the algorithm-based rules resulted in a low dropout rate. Most importantly, algorithm-guided antidepressive treatment showed a favorable response in those depressed patients who were treated according to the SSTR protocol.

Algorithms↗

PubMedDate not supplied

Association between response to lithium augmentation and the combined DEX/CRH test in major depressive disorder.

Although lithium augmentation is the foremost and most well-documented treatment strategy for treatment resistant depression, knowledge of factors related to response remains scanty. Findings with the combined dexamethasone/corticotropin-releasing hormone (DEX/CRH) test are associated with response to treatment with a tricyclic antidepressant. This study investigated the potential predictive value of the DEX/CRH test for lithium augmentation response in major depressive disorder. The DEX/CRH test was conducted prior to lithium augmentation in 30 patients with a major depressive episode who had not responded to an antidepressant monotherapy trial of at least 4 weeks. Response status was assessed weekly using the Hamilton Rating Scale for Depression. For multivariate prediction, a logistic regression analysis was performed. Eleven (37%) patients responded to lithium augmentation within 4 weeks. Responders showed higher ACTH response and lower cortisol response in the DEX/CRH test, but results were not statistically significant. However, non-responders had a statistically significant higher cortisol/ACTH peak ratio (3.43+/-1.75) compared to responders (2.18+/-1.38) (P=0.027). This ratio is an indicator for the sensitivity of the adrenal cortex to ACTH. A cortisol/ACTH peak ratio of 1.8 was identified as the best cutoff point to differentiate responders from non-responders. In conclusion, results suggest a more sensitive adrenal cortex in non-responders to lithium augmentation. The findings would be in line with the assumption of a more chronic course of depression with more pronounced biological alterations in the non-responder group, because chronic depression is known to cause enlargement of the adrenal gland with a subsequent hypersensitivity to ACTH. Results of this study should be confirmed in a larger study group.

Adrenocorticotropic Hormone↗