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Anne Berghöfer

Publications and source records attributed to Anne Berghöfer.

18 recordsLinked to original sources

The impact of lithium long-term medication on suicidal behavior and mortality of bipolar patients.

The article reviews the existing evidence and the concept of the anti-suicidal effect of lithium long-term treatment in bipolar patients. The core studies supporting the concept of a suicide preventive effect of lithium in bipolar patients come from the international research group IGSLI, from Sweden, Italy, and recently also from the U.S. Patients on lithium possess an eight- time lower suicide risk than those off lithium. The anti-suicidal effect is not necessarily coupled to lithium's episode suppressing efficacy. The great number of lives potentially saved by lithium adds to the remarkable benefits of lithium in economical terms. The evidence that lithium can effectively reduce suicide risk has been integrated into modern algorithms in order to select the optimal maintenance therapy for an individual patient.

Algorithms↗

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↗

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↗

Bone mineral density during maintenance treatment with supraphysiological doses of levothyroxine in affective disorders: a longitudinal study.

BACKGROUND: This prospective study was designed to determine whether patients with prophylaxis-resistant affective disorders, receiving adjunctive maintenance therapy with supraphysiological doses of levothyroxine (L-T4), show evidence of accelerated bone loss compared to the reference population database. METHODS: In 21 patients, bone mineral density (BMD) of the spine (lumbar vertebrae L1-L4) and femur (femoral neck, trochanter, and Ward's triangle) was measured by dual energy X-ray absorptiometry (DXA). BMD measurement was performed first after patients had been on thyroid-stimulating hormone (TSH)-suppressive therapy with L-T4 (mean dose=411 mcg/d) for an average of 16.4 months and again after 33.6 months of L-T4 (mean dose=416 mcg/d) therapy. RESULTS: There was no statistically significant difference between the actual percentage decline in bone mineral density and the expected percentage decline in any of the measured bone regions. In a stepwise linear regression analysis, age was identified as a predictor of percentage change in BMD. After controlling for age, the only other variable that showed a consistent trend was the dose of L-T4, with higher doses being positively correlated with the percentage decline of BMD. LIMITATIONS: Relatively small sample size, no bone density assessment prior to treatment with L-T4, no patient control group with mood disorders who did not receive L-T4 treatment, and bone density follow-up intervals were variable. CONCLUSIONS: This study did not demonstrate evidence that long-term treatment of affectively ill patients with supraphysiological doses of L-T4 significantly accelerates loss of bone mineral density compared to the age-matched reference population. However, the decline of BMD in one individual patient underscores that caution is indicated and that regular assessment of BMD during longer-term supraphysiological thyroid hormone treatment is needed.

Absorptiometry, Photon↗

Prophylaxis of schizoaffective disorder with lithium or carbamazepine: outcome after long-term follow-up.

OBJECTIVES: This study was conducted (1) to assess the prophylactic efficacy of lithium and carbamazepine in the maintenance treatment of schizoaffective disorder (SAD) with long-term follow-up, (2) to find predictors of the success or failure of prophylaxis, and (3) to search for differences in outcome between schizoaffective patients diagnosed according to either ICD-10 or DSM-IV. METHODS: Participating patients met the ICD-10 and/or DSM-IV criteria for schizoaffective disorder. Outcome was assessed using the Morbidity Index and time elapsed until the first recurrence during prophylaxis. Predictor variables were age at onset of illness, gender, and family history, as well as the following parameters prior to prophylaxis: time between onset of illness and start of prophylactic treatment (latency), severity of illness (hospitalization rate), number of hospital admissions and polarity of schizoaffective disorder (schizobipolar vs. schizounipolar). The time spent in the hospital per year was used to compare the course of illness before maintenance therapy to the time during maintenance therapy. Co-medication was taken into account. The clinical data during prophylaxis were ascertained prospectively. RESULTS: Forty-nine patients met the ICD-10 criteria for schizoaffective disorder, 34 of whom also met the DSM-IV criteria. All 49 patients underwent prophylactic therapy with either lithium (n=41) or carbamazepine (n=8) for an average of 6.8 years. After initiating prophylaxis, the number of days spent in the hospital declined dramatically from an average of 71 days to 11 days per year. No independent variable proved to be a consistent predictor of the course of treatment. In regard to the subgroup of patients diagnosed according to DSM-IV, no significant differences were observed when this subgroup was compared to the whole sample. LIMITATIONS: As this is a naturalistic study it does not allow for exact quantitative measures of effectiveness. CONCLUSIONS: This study is the first of its kind to investigate the efficacy of maintenance therapy in SAD over such an extended period of time. The results of the study show that lithium and carbamazepine appear to be highly effective in treating patients with schizoaffective disorder. However, it remains unclear how many schizoaffective patients will respond to mood stabilizer treatment and whether predictors of clinical relevance exist. In our sample, differences in the ICD-10 and DSM-IV diagnostic criteria for schizoaffective disorder were not related to significant differences in clinical outcome.

Adult↗

Platelet-5HT uptake and gastrointestinal symptoms in patients suffering from major depression.

The objective of this study was to determine whether the presence of gastrointestinal symptoms, as defined by item 12 of Hamilton-Rating-Scale for Depression, is related to kinetic characteristics of platelet-5HT uptake in patients with major depression. The clinical picture of depression in patients with severe form of appetite loss with difficulties of eating (item 12 = 2) and weight loss was characterized by the combination of depressed mood with somatic symptoms of anxiety, sleep disturbances, decreased activity and the presence of nausea. The high frequency of relatively low Vmax and Km of 5HT uptake in this group (n = 12), all in the lower range of controls, resulted in significantly lower mean values compared with patients without gastrointestinal symptoms (n = 16; item 12 = 0) or 57 healthy subjects (Vmax = 1.36 +/- 0.27 vs. 2.14 +/- 0.85 vs. 2.05 +/- 0.74 nMol 5HT/10(9)plat.x min; Km = 382 +/- 68 vs. 467 +/- 94 vs. 492 +/- 123 nM respectively). Although our finding needs confirmation, it seems that in the research for serotonergic mechanisms in major depression, it makes sense to look at depressed patients with or without somatic symptoms separately. Based on findings in 5HT transporter knock-out mice (J. Neurosci. 15 (2001) 6348), we assume that the low apparent Vmax of platelet-5HT uptake reflects the low expression of 5HT transporter not only in platelets, but also in the gut mucosa and enteric serotonergic neurons, which probably increases the risk of typical gastrointestinal symptoms such as appetite loss and nausea occurring in some depressed patients.

Adult↗

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↗

The antisuicidal and mortality-reducing effect of lithium prophylaxis: consequences for guidelines in clinical psychiatry.

The suicide-related mortality among patients with affective disorders is approximately 30 times higher, and overall mortality 2 to 3 times higher, than suicide-related mortality in the general population. Lithium has demonstrated possibly specific antisuicidal effects apart from its prophylactic efficacy: it significantly reduces the high excess mortality of patients with affective disorders. To date, suicide-prevention effects have not been shown for antidepressant or anticonvulsant long-term treatment. Clozapine appears to reduce the suicide rate in schizophrenia patients. Against this background, guidelines and algorithms for selecting an appropriate prophylactic strategy for affective disorders should consider the presence of suicidality in patient history. Appropriate lithium prophylaxis prevents approximately 250 suicides yearly in Germany, although lithium salts are infrequently prescribed within the National Health Scheme (specifically, to 0.06% of the population). Rational treatment strategies most likely would demand that prescription rates be about 10 times higher.

Algorithms↗

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↗

Effectiveness and outcome predictors of long-term lithium prophylaxis in unipolar major depressive disorder.

OBJECTIVE: To determine the effectiveness of lithium prophylaxis in unipolar major depressive disorder (MDD) and to identify predictors of outcome including comedication. METHODS: In this long-term naturalistic study, clinical data from 55 patients with MDD (DSM-III-R) were collected prospectively in an outpatient clinic specializing in the treatment of affective disorders. OUTCOME MEASURES: Change in hospital admission rate (number and duration) during prophylaxis compared with the period before prophylaxis, Morbidity-Index during prophylaxis and time to first recurrence after initiation of lithium treatment. RESULTS: During an average follow-up period of 6.7 years, a significant decline in the number of days spent in hospital (p<0.001; 52 d/yr less; 95; CI 31-73 d) and a low Morbidity-Index (mean 0.07) was observed. Only in 6 patients did medication have to be changed because of side-effects (n=4) or a lack of efficacy (n=2). None of the independent variables we analyzed proved to be important in predicting the outcome of lithium prophylaxis. Comedication was necessary in 21 patients. The overall outcome of their prophylactic treatment, however, did not differ from the group that did not receive comedication in the symptom-free intervals. CONCLUSIONS: The results of this study, with its long observation period and the inclusion of comedication as a confounding variable, indicate that lithium is a potent prophylactic agent for unipolar MDD in a naturalistic setting. In contrast to the findings of others, age was not associated with the outcome of prophylaxis, and latency did not predict outcome. Contrary to doubts that have been raised in recent years with regard to the effectiveness of lithium in everyday clinical practice, lithium appears to be a safe and potent alternative to antidepressants.

Adult↗

Effects of supraphysiological doses of L-thyroxine on cognitive function in healthy individuals.

Cognitive disturbance is commonly associated with disorders of the thyroid gland, particularly hypothyroidism, and usually subsides following thyroid hormone replacement therapy. In contrast, the effects of thyroid hormones on cognitive functions in healthy individuals have rarely been studied. The goal of this open-label study was to investigate the short-term effects (duration of administration 45 days on average) of supraphysiological doses of L-thyroxine (L-T(4)) on cognitive performance in young, euthyroid, healthy subjects. Eleven subjects performed a comprehensive neuropsychological test battery, once without and once during administration of supraphysiological doses of L-T(4). There were no significant differences in any of the cognitive test results between the two test sessions. The results of this study do not support our working hypothesis that thyroid hormone can change cognitive performance in young, euthyroid, healthy individuals.

Adult↗

Correlation between serotonin uptake in human blood platelets with the 44-bp polymorphism and the 17-bp variable number of tandem repeat of the serotonin transporter.

Dysfunctions of the central serotonin (5-hydroxytryptamine, 5-HT) system seem to be associated with psychiatric disorders such as schizophrenia or depression. Previous studies suggested that a 44-bp insertion/deletion polymorphism of the 5-HT transporter (5-HTT) promoter region might influence the transcriptional activity of the 5-HTT gene, and the insertion variant resulted in increased 5-HTT expression and 5-HT uptake. Moreover, a 17-bp variable number of tandem repeat (VNTR) polymorphism of the second intron may act as a transcriptional regulator with allele dependent differential enhancer-like properties. Since the 5-HTT of human platelets shares many properties with the transporter of neural tissue, platelets are widely used as a surrogate tissue source, possibly reflecting central 5-HT metabolism. Therefore, we investigated the impact of the 44-bp polymorphism and the 17-bp VNTR for 5-HT uptake in platelets of 50 male subjects. We found no significant effect of the 44-bp polymorphism and of the 17-bp VNTR on maximum rate (Vmax) of 5-HT uptake. However, individuals homozygous for the 5-HTT intron 2 allele with 12 repeats (STin2.12) of the 17-bp VNTR appeared to have lower affinity of 5-HT uptake than individuals heterozygous for the STin2.10/STin2.9 allele. This was also observed for the combined analysis of both polymorphisms. In conclusion, we found no association between the different genotypes of the 44-bp polymorphism and the 17-bp VNTR and maximum rate of 5-HT uptake into platelets.

Adult↗

Bipolar disorder.

Bipolar, or manic-depressive, disorder is a frequent, severe, mostly recurrent mood disorder associated with great morbidity. The lifetime prevalence of bipolar disorder is 1.3 to 1.6%. The mortality rate of the disease is two to three times higher than that of the general population. About 10-20% of individuals with bipolar disorder take their own life, and nearly one third of patients admit to at least one suicide attempt. The clinical manifestations of the disease are exceptionally diverse. They range from mild hypomania or mild depression to severe forms of mania or depression accompanied by profound psychosis. Bipolar disorder is equally prevalent across sexes, with the exception of rapid cycling, a severe and difficult to treat variant of the disorder, which arises mostly in women. Because of the high risk of recurrence and suicide, long-term prophylactic pharmacological treatment is indicated. Lithium salts are the first choice long-term preventive treatment for bipolar disorder. They also possess well documented antisuicidal effects. Second choice prophylactic treatments are carbamazepine and valproate, although evidence of their effectiveness is weaker.

Anticonvulsants↗

Effects of supraphysiological thyroxine administration in healthy controls and patients with depressive disorders.

BACKGROUND: Thyroxine (T(4)) in supraphysiological doses has been found to be an effective supplemental treatment in open studies for refractory mood disorders. Unexpectedly, only minimal side effects have been reported. The goal of the present study was to investigate whether healthy controls and depressed patients differ in their ability to tolerate supraphysiological doses of T(4). METHODS: This was an 8-week open study to investigate side effects and levels of thyroid hormones in 13 healthy controls and to compare results with those of 13 patients with refractory depression (unipolar and bipolar) undergoing the similar procedures and T(4) dosing regimen in a previous augmentation study. RESULTS: The rate of discontinuation due to side effects was significantly higher in the control group than for the patients (38% versus 0%). The severity of the side effects in the controls increased significantly during treatment with T(4). The side effect scores of the patients were higher than those of the controls prior to T(4) treatment, but did not change significantly during the treatment period. Although the serum concentrations of thyroid hormones rose significantly in both groups, concentrations of fT(3) and fT(4) were significantly higher in the controls. CONCLUSIONS: Healthy controls and depressed patients respond significantly differently to supraphysiological T(4). Healthy controls experience higher elevations of thyroid hormones in response to supraphysiological T(4), thus inducing significantly more side effects and discontinuation. LIMITATIONS: Open-label study; groups were studied at different times; in contrast to healthy controls, depressed patients were also taking antidepressants. CLINICAL RELEVANCE: Studies provide safety and tolerability data on treatment with supraphysiological doses of T(4).

Adult↗

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↗

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↗

Initial lithium and valproate combination therapy in acute mania.

Early onset of treatment efficacy is especially important for severe mania syndromes. Lithium has usually a delayed onset of response, which is disadvantageous for inpatient treatment of severe mania. Valproate is effective in treating acute mania and has sedative properties. It has, however, a response rate of approximately only two thirds. Therefore, the initial combination of valproate and lithium was evaluated in a prospective case series of 12 patients, and a retrospective analysis was carried out for 5 patients in comparison with a pretreatment period when lithium therapy was applied without valproate. Outcome criterion for analysis was the latency of response and remission, as well as the amount of neuroleptics used for additional sedation. Patients had a mania syndrome-severity score comparable with the mean mania score of the bipolar manic patients treated in the same unit. All patients under the combination treatment responded. The response occurred within a shorter time compared with the lithium pretreatment episode, which is statistically marginally significant, and the use of neuroleptic medication could be markedly reduced from 18,601.6 mg chlorpromazine equivalents to 3,927.6 mg (p < 0.025). The initial valproate-lithium combination therapy seems to be a safe and effective way to treat severe mania syndromes in the clinic.

Acute Disease↗

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↗