Schizotypy, affective temperaments and anhedonia in bipolar depression. / Schizotypia, temperamenty afektywne i anhedonia w depresji dwubiegunowej.

OBJECTIVES: "Schizotypy" is a term describing personality traits reflected in emotional, perceptual and cognitive styles. Affective temperaments are trait-like features which were observed to be stable in time and predispose to mood disorders. The purpose of this study was to examine relationship between schizotypal features, affective temperaments and anhedonia in patients with bipolar depression. METHODS: 54 patients with bipolar depression were included in the study. Participant were administered the following psychometric tools: Dimensional Anhedonia Rating Scale (DARS), Snaith-Hamilton Pleasure Scale (SHAPS), Oxford-Liverpool Inventory of Feelings and Experiences (O-LIFE), Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire (TEMPS-A), and Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-SR). Correlations between the variables were calculated and linear regression models were built. RESULTS: Only hyperthymia (affective temperament) and introvertive anhedonia (schizotypal domain) were statistically significantly correlated with anhedonia. In regression models, introvertive anhedonia predicted higher whereas hyperthymic features lower severity of anhedonia (measured by the SHAPS scale). CONCLUSIONS: Hyperthymic features are protective and introvertive anhedonia is a risk factor for consummatory anhedonia.

TED-trazodone effectiveness in depression: a naturalistic study of the effeciveness of trazodone in extended release formulation compared to SSRIs in patients with a major depressive disorder.

Introduction: Selective serotonin reuptake inhibitors (SSRIs) are the most often used medications to treat major depressive disorder (MDD). Despite their effectiveness in reducing depressive symptoms, several issues are associated with their use in MDD, such as limited improvement of anhedonia, emergence of emotional blunting, induction or exacerbation of insomnia, and sexual dysfunction. Due to its also devoid of the issues related to treatment noted with SSRIs. The aim of this 12-week non-inferiority naturalistic observation was to compare the effectiveness and tolerability of SSRIs and trazodone in extended release (XR) in MDD. Methods: A total of 186 subjects were recruited, of which 92 received trazodone XR and 94 received SSRIs. Patients were allocated to trazodone XR or SSRIs, according to the attending physician based on clinical evaluation. Assessments at baseline and weeks 2, 4, 8, and 12 were conducted to evaluate the severity of depression (Montgomery-Åsberg Depression Rating Scale, clinician- and patient-rated Quick Inventory of Depressive Symptomatology-the primary endpoints of the study), anhedonia (the Snaith-Hamilton Pleasure Scale), anxiety (the Hamilton Anxiety Rating Scale), insomnia (the Athens Insomnia Scale), and therapeutic effectiveness (the Clinical Global Impression Scale). Results: After 12 weeks, trazodone XR was more effective than SSRIs in reducing the severity of depression, anxiety, and insomnia. There was a trend for higher effectiveness of in reduction of anhedonia, which became insignificant after controlling the results for the duration of previous psychiatric treatment as a covariate. The proportion of treatment-responsive subjects in the trazodone XR group compared to SSRIs was comparable or higher. The proportion of patients achieving remission was higher in the trazodone XR arm vs. the SSRI arm. Discussion: In summary, the results indicate that trazodone XR is effective in MDD in the "real-world" setting. Its potential superiority over SSRIs in addressing particular symptomatic dimensions should be verified in future studies.

Polish adaptation of the Dimensional Anhedonia Rating Scale (DARS) - validation in the clinical sample.

Background: Anhedonia is the core symptom of depression. Its presence has been linked to worsened prognosis. The Dimensional Anhedonia Rating Scale (DARS) is a scale measuring desire, motivation, effort and consummatory pleasure across different domains. The aim of this paper was to confirm factor structure, assess reliability and validity of the Polish adaptation of the DARS in a clinical sample of patients with mood disorders and healthy controls (HC). Methods: The study sample included 161 participants aged 18-65 years - 34 HC, 72 patients with bipolar disorder and 55 with major depressive disorder (in depressive episode or remission). Reliability of the Polish adaptation of the DARS was assessed using Cronbach's α and the average inter-item correlation (AIC). Convergent and divergent validity was established by Pearson's correlations between the DARS and the Snaith-Hamilton Pleasure Scale (SHAPS), the Quick Inventory of Depressive Symptomatology- self-report (QIDS-SR), the Hospital Anxiety and Depression Scale (HADS). The structure of the scale was examined by factor analysis. Results: The factor structure was consistent with the original scale. Strong internal consistency for the DARS total score (Cronbach's α = 0.95) and all subscales (0.86-0.93) was observed. The DARS demonstrated good convergent (moderate to strong correlations with measures of anhedonia and depression) and divergent validity (weak correlations with anxiety level). Conclusion: The Polish DARS demonstrated excellent internal consistency and very good validity. The scale is a valuable contribution to the psychometrics of anhedonia measures in patients with mood disorders.

When practice does not make a perfect - paradoxical learning curve in schizophrenia and bipolar disorder revealed by different serial reaction time task variants.

Introduction: Our previous studies identified a paradoxical implicit motor learning curve in schizophrenia (SZ) and bipolar disorder (BD) patients. This study aimed to verify whether those previously observed deficits may be captured by a new version of the ambidextrous serial reaction time task (SRTT), prepared for use in the MRI. Methods: This study involved 186 participants. A total of 97 participants (33 BD, 33 SZ, and 31 healthy controls, HCs) completed the original, unlimited time response variant of SRTT. A total of 90 individuals (30 BD, 30 SZ, and 30 HCs) underwent a newer, limited response time version of this procedure. Results: There was no significant difference in terms of implicit motor learning indices between both limited and unlimited response time SRTT. Compared to HCs, SZ, and BD patients presented decreased indices of implicit motor learning. Both clinical groups showed a paradoxical learning pattern that differed significantly from the HCs. Moreover, in the SZ group, the pattern depended on the hand performing SRTT. Discussion: The limited response time SRTT variant allowed us to replicate the findings of disrupted implicit motor learning in SZ and BD. The use of this paradigm in further neuroimaging studies may help to determine the neuronal underpinnings of this cognitive dysfunction in the abovementioned clinical groups.

Lurasidone Augmentation of Clozapine in Schizophrenia-Retrospective Chart Review.

The aim of our study was to evaluate the effectiveness of lurasidone augmentation of clozapine in treatment-resistant schizophrenia (SZ) in a retrospective chart review. From the medical records of 916 SZ patients, we identified 16 individuals treated with a combination of clozapine and lurasidone. The detailed clinical data are described separately for each patient. We compared the Clinical Global Impression-Severity (CGI-S) scores between three points of observation: before the treatment and one month and two months after its initiation. CGI Improvement (CGI-I) scores were used to evaluate the treatment response between the first and last points of observation. The vast majority of patients (14/16, 87.5%) responded to lurasidone augmentation of clozapine (CGI-I scores 1 or 2). Therapeutic effects were observable after 3-12 weeks of treatment (median 6 (4-6)). A reduction in CGI-S scores was observed after the first month of observation. There was an observable reduction in positive, depressive and anxiety symptoms, as well as an improvement in psychosocial functioning. Two patients discontinued treatment due to side effects. Our study suggests that lurasidone augmentation of clozapine may lead to improvements in a broad range of SZ symptom dimensions.

Predictors of treatment response to serotonin and noradrenaline reuptake inhibitors in fibromyalgia.

INTRODUCTION: Fibromyalgia (FM) is often comorbid with anxiety and depression. Serotonin and noradrenaline reuptake inhibitors (SNRIs) are used in the treatment of FM, depression, and anxiety, but they are ineffective in a substantial number of patients. Recently, it has been reported that FM is associated with impaired glucose metabolism. OBJECTIVES: The aim of the study was to explore the associations between insulin resistance, psychiatric comorbidities, and treatment response to SNRIs in patients with FM. PATIENTS AND METHODS: A total of 59 patients with FM and 30 healthy controls (HCs) were recruited. The study patients were classified as treatment­nonresponsive if the SNRI treatment resulted in a reduction in reported pain by less than 30%. All participants were examined by a physician and completed self­report questionnaires. Blood samples were drawn to assess fasting glucose and insulin levels and to calculate the Homeostatic Model Assessment of Insulin Resistance (HOMA­IR) values. Multivariable logistic regression models were constructed to analyze the associations between insulin resistance, psychiatric comorbidies, and the lack of response to treatment with SNRIs. RESULTS: The SNRI nonresponders (FM [T-]) had higher body mass index (BMI), fasting insulin level, and HOMA­IR values than the responders (FM [T+]) and HCs. The FM [T+] patients did not significantly differ from HCs in terms of BMI, levels of fasting glucose and fasting insulin, and HOMA­IR values. Depression, anxiety, and personality disorders were significantly more prevalent in the FM [T-] than in the FM [T+] group. Insulin resistance, depression, anxiety, and personality disorders were identified as the predictors of nonresponse to SNRI treatment. The effect of BMI on the lack of response to SNRIs was fully mediated by insulin resistance. CONCLUSIONS: Increased values of certain clinical and metabolic parameters (BMI, fasting glucose, fasting insulin, HOMA­IR) as well as the presence of psychiatric comorbidities could affect the response to treatment with SNRIs in the patients with FM.

TED-Trazodone Efficacy in Depression: A Naturalistic Study on the Efficacy of Trazodone in an Extended-Release Formulation Compared to SSRIs in Patients with a Depressive Episode-Preliminary Report.

These are the preliminary results of a 12-week non-randomized, open-label, non-inferiority study comparing the effectiveness of trazodone in an extended-release formulation (XR) versus SSRIs in the treatment of major depressive disorder (MDD). Participants (n = 76) were recruited, and 42 were assigned to the trazodone XR group and 34 to the SSRIs group. The choice of drug was based on clinical presentation and relied upon the attending physician. Assessments were made at five observation time points, at the following weeks: 0, and after 2, 4, 8, and 12 weeks. The evaluations included: symptoms of depression (MADRS, QIDS-clinician, and self-rated versions-primary study endpoints), anhedonia (SHAPS), anxiety (HAM-A), insomnia (AIS), psychosocial functioning (SDS), and therapeutic efficacy (CGI). At baseline, the trazodone group had significantly more severe depressive, anxiety, and insomnia symptoms and worse psychosocial functioning compared to the SSRIs group. After 12 weeks, trazodone XR was more effective than SSRIs in reducing the severity of insomnia and depression. There were no differences between the groups in the frequencies of therapeutic response and remission, which indicated the non-inferiority of the trazodone XR treatment. In conclusion, our results showed that in a "real world" setting, trazodone XR is effective in the treatment of patients with MDD.

Cariprazine augmentation of clozapine in schizophrenia-a retrospective chart review.

The aim of our study was to evaluate the efficacy of cariprazine augmentation of clozapine in treatment-resistant schizophrenia in a retrospective chart review. Among 916 medical records of schizophrenia patients, we identified 12 individuals treated with a combination of those drugs for a duration of 3-60 weeks [median 32 (10-40)]. Clinical Global Impression-Improvement (CGI-I) scores were used to measure the treatment response between the introduction of cariprazine augmentation of clozapine and the last point of observation. The majority of the patients presented treatment response (9/12 patients, 75%) after 4-16 weeks of therapy [median 6 (4-12)]. Treatment was associated with the decrease in positive, negative, affective, and anxiety symptom severity, as well as improvement of patient global functioning. One patient discontinued the treatment due to side effects (akathisia), and two patients halted the therapy due to the exacerbation of psychotic symptoms. Our study presents a thorough clinical description of the largest number of treatment-resistant schizophrenia patients medicated using cariprazine augmentation of clozapine in a "real-world" setting. Our results suggest that the use of this combination may lead to the improvement in a broad range of symptoms of patients with this condition.

TED (Trazodone Effectiveness in Depression): effectiveness of trazodone extended-release in subjects with unsatisfactory response to SSRIs. / TED (Trazodone Effectiveness in Depression): efektywnosc trazodonu o przedluzonym uwalnianiu u pacjentów z niezadowalajaca odpowiedzia na leczenie SSRI.

OBJECTIVES: Selective serotonin reuptake inhibitors (SSRIs) are the most commonly used drugs to treat major depressive disorder (MDD). However, about 50% of MDD patients do not achieve treatment response to SSRIs and there is little evidence on which drugs are effective as second-line treatment in those who do not respond to SSRIs. METHODS: In this work, the data of 79 patients with MDD were analyzed to evaluate the effectiveness of trazodone XR in the group of individuals treated de novo and those switched to trazodone XR after failed treatment attempt with SSRIs. The assessments were performed at baseline and weeks 2, 4, 8 and 12 using tools to evaluate the degree of: depression (Montgomery-Åsberg Depression Rating Scale, clinician and patient-rated Quick Inventory of Depressive Symptomatology - the primary endpoints of the study), therapeutic effectiveness (Clinical Global Impression Scale), anhedonia (Snaith-Hamilton Pleasure Scale), anxiety (Hamilton Anxiety Rating Scale), insomnia (Athens Insomnia Scale), psychosocial functioning (Sheehan Disability Scale) and sexual functioning (Female Sexual Function Inventory in women/International Index of Erectile Function in men). RESULTS: The rates of treatment response and remission were largely similar in both studied groups. CONCLUSIONS: The results showed that effectiveness of trazodone XR in the treatment of patients with MDD who did not respond to SSRIs administered as first-line treatment of a particular depressive episode was comparable to that noted in patients treated de novo. Furthermore, trazodone XR effectively improved depression, anxiety, insomnia, anhedonia and psychosocial functioning in both studied groups. Additionally, trazodone XR as secondline treatment improved sexual functions in male subjects previously treated with SSRIs.

Case Report: Vortioxetine in the Treatment of Depressive Symptoms in Patients With Epilepsy-Case Series.

Epilepsy and depression are both serious and potentially disabling conditions which often coexist-bidirectional relationship between the two disorders has been observed. Comorbidity between depression and epilepsy can be attributed to: underlying common pathophysiological mechanisms, psychiatric side effect of antiepileptic medications and psychological response to stress in people with chronic, neurological condition. Despite high prevalence of depressive symptoms in patients with epilepsy, current evidence of the effectiveness of antidepressant therapy in this group of patients is very limited. Vortioxetine is an antidepressant with multimodal activity, very good treatment tolerability, low risk of inducing pharmacokinetic interactions, relative safety of treatment in patients with somatic comorbidities, low risk of causing: sedation, sexual dysfunctions and metabolic side effects. Vortioxetine seems to be a promising treatment option for depressed patients with cognitive dysfunctions, anhedonia and anxiety. In this case series, we report nine cases of patients with epilepsy and depressive symptoms treated with vortioxetine. Seven cases are patients with secondary focal and generalized epilepsy and two with unclassified epilepsy. Three patients presented with depressive episode in the course of bipolar disorder and six patients had depressive symptoms due to organic mood disorder. The dose range of vortioxetine was between 10 and 20 mg. In all of the presented cases effectiveness and tolerability of treatment were very good. Remission of depressive symptoms was achieved in all patients. No epilepsy seizures after switch to vortioxetine were observed in seven cases. In two patients seizures occurred during the first months of vortioxetine treatment but this most probably was due to suboptimal antiepileptic treatment-satisfactory seizure control was achieved after optimization of antiepileptic pharmacotherapy. Vortioxetine was discontinued in two of the presented cases due to pregnancy planning. The duration of observation period during vortioxetine therapy ranged from 2 to 48 months. In conclusion, vortioxetine can be a promising treatment option in patients with epilepsy and comorbid depressive symptoms.

Lurasidone in Therapy of Treatment-resistant Ultra-rapid Cycling Bipolar Disorder: Case Report.

Lurasidone is an atypical antipsychotic approved for the treatment of schizophrenia and bipolar depression. It seems to have a favorable metabolic profile and low risk of causing adverse interactions. Here we present a case of a 25-year old female patient with treatment-resistant ultra-rapid cycling bipolar disorder, obesity, hypothyroidism, and epilepsy. Because of predominant depressive symptoms, occasional occurrence of brief psychotic symptoms and patient's somatic comorbidities, treatment with lurasidone was initiated. Clinical improvement was observed 3 weeks and cessation of ultra-rapid cycling course of the disease 8 weeks after the beginning of lurasidone treatment. The patient's level of functioning improved and body mass significantly decreased, with good tolerance of the pharmacotherapy. Lurasidone seems to be a promising treatment option in patients with treatment-resistant rapid cycling bipolar disorder.

Withdrawal Symptoms Following Discontinuation of Vortioxetine-Retrospective Chart Review.

The efficacy of vortioxetine has been proven in many studies, but data concerning discontinuation symptoms (DS) after vortioxetine withdrawal is scarce. The aim of our study is to systematically evaluate the prevalence, determinants, and clinical features of vortioxetine DS in a retrospective chart review. Data were obtained from medical records of 263 adult patients with depressive disorders who discontinued former vortioxetine treatment. DS were observed in eight (3%) patients after 71-375 days (median 272) of treatment. DS emerged after median three days following vortioxetine withdrawal and lasted for median seven days. The clinical presentation of DS involved: emotional lability (100% of patients), irritability (75%), sudden worsening of mood (75%), nervousness (37.5%), and agitation (37.5%). Median DESS score was four (range of four to six). DS were significantly more prevalent after accidental vs. planned discontinuation (adjusted p = 0.011) and were less frequent after switching to a different antidepressant vs. ceasing pharmacotherapy (adjusted p = 0.0165). DS appeared more often if patients discontinued therapy without medical consultation (adjusted p = 0.033). The occurrence of DS was not associated with the dose and way of drug discontinuation (sudden vs. gradual). In sum, our results show that clinicians should be aware that vortioxetine withdrawal is associated with the possibility of DS.

Adverse effects of interactions between antipsychotics and medications used in the treatment of cardiovascular disorders.

BACKGROUND: High level of comorbidity between bipolar disorder or schizophrenia and cardiovascular diseases (CVD) in clinical practice may contribute to drug-drug interactions between medications used in these conditions. The aim of this study was to evaluate harmful interactions between antipsychotics and medications used in treatment of CVD. METHODS: The analysis of 52 cases of adverse reactions with a clinical picture indicates that they were the result of the combination of antipsychotic with cardiovascular medications. RESULTS: The highest number of interactions with antipsychotics was recorded among beta-blockers (n = 13, 25% of all cases), including cardiac arrhythmias [atrial fibrillation (n = 1): risperidone plus atenolol; bradycardia (n = 1): perphenazine with metoprolol; ventricular arrhythmias: sertindole with metoprolol (n = 1) and ziprasidone with sotalol (n = 3)] and hypotension [chlorprotixene with nebivolol or metoprolol (n = 2)]. 12 cases concerned statins-myalgia, myopathy, or creatine kinase elevation appeared after combination of atorvastatin with haloperidol (n = 1), quetiapine (n = 3) or risperidone (n = 1), and simvastatin with quetiapine (n = 5) or risperidone (n = 2). There were also cases of interactions observed for the use of antipsychotics with anti-arrhythmic drugs (amiodarone, flecainide, propafenone) (n = 11), calcium channel blockers (n = 6), and other cardiac medications: clonidine, dabigatran, doxazosin, ivabradine, and losartan (n = 10). CONCLUSIONS: Due to a high risk of interactions and related adverse effects, particular attention should be paid while using cardiovascular medications with antipsychotics. Clinical decisions should be preceded by a detailed analysis of safety, risk-benefit ratio to search for, as safe as possible, drug combinations.

Adverse effects of interactions between antidepressants and medications used in treatment of cardiovascular disorders. / Niepozadane efekty interakcji leków psychotropowych z produktami leczniczymi stosowanymi w chorobach ukladu sercowo-naczyniowego.

OBJECTIVES: To evaluate harmful interactions between antidepressants and medications used in treatment of cardiovascular disorders. METHODS: The analysis of 66 cases of adverse reactions with a clinical picture indicating, to a degree that is probable or certain, that they were the result of the combination of antidepressant with cardiovascular medication. RESULTS: The most common side effect (n = 25, 37.9%) was bradycardia (and other side effects of beta blockers) as a consequence of addition of metoprolol or propranolol to SSRI or bupropion. In one case combination of fluoxetine with propranolol resulted in cardiac arrest. We observed 8 cases of intensified side effects of amlodipine (swelling of lower limbs, headaches) after its combination with: fluoxetine, sertraline and paroxetine, and occurrence of myalgia, elevated aminotransferase levels, polyuria and hypotension after combination of lercanidipine with some of the SSRIs. We also found i.a. worsening of propafenone tolerance in combination with venlafaxine or bupropion, 2 cases of granulopenia associated with duloxetine-propafenone combination, 2 cases of hemorrhagic complications associated with the combination of vortioxetine-warfarin, 1 case of hyponatremia associated with the combination of vortioxetine and hydrochlorothiazide, as well as antagonizing clonidine's hypotensive effect by mirtazapine, and peripheral thrombosis following the combination of warfarin with trazodone. CONCLUSIONS: Because of ahigh risk of interactions and related adverse effects, especially in older patients, each decision regarding combination of a particular antidepressant with a medication used in treatment of cardiovascular disorders should be preceded by a detailed analysis of safety and risk-benefit ratio, and also be associated with the search for the safest, alternative combinations of the above-mentioned medications.