Clinical features and predictors of non-response in severe catatonic patients treated with electroconvulsive therapy.

OBJECTIVE: To explore the demographic and clinical features of severe catatonic patients, comparing responders and non-responders to ECT in order to detect possible predictors of non-response. METHODS: This naturalistic study included 59 catatonic inpatients with a diagnosis of mood disorder according to DSM-IV-TR criteria. All patients were treated with bilateral ECT and evaluated before and after ECT course. The response to ECT was defined as a Clinical Global Impression (Improvement subscale) rating 1 'very much improved' or 2 'much improved'. Clinical variables were compared between responders and non-responders; logistic regression was used to predict the probability of non-response, with regard to the symptoms presented by the patients. RESULTS: The response rate was 83.1%. Non-responders (n = 10) to ECT showed neurological comorbidities, treatments with dopamine agonists and anticholinergic drugs, waxy flexibility, and echophenomena more frequently than respondents (n = 49). Echophenomena resulted a significant predictor of non-response in the multivariate analysis. CONCLUSION: In line with previous reports, ECT resulted effective in the vast majority of severe catatonic patients. The association between ECT resistant catatonia and neurological comorbidity, use of dopamine-agonist and anticholinergic medications is consistent with the hypothesis that ECT is more effective in 'top-down' than in 'bottom-up' variant of catatonia.Key pointsCatatonic symptoms are frequently associated with severe and psychotic mood disorders.Electroconvulsive therapy is effective in treating most forms of severe catatonia.Neurological comorbidity and the presence of 'echopraxia/echolalia' could represent predictors of non-response to ECT.

Relationships Among Delayed Sleep Phase Disorder, Emotional Dysregulation, and Affective Temperaments in Adults With Attention Deficit Hyperactivity Disorder and Cyclothymia.

This study aims to explore the relationships between delayed sleep phase disorder (DSPD) and emotional dysregulation in 240 patients (134 with cyclothymia, 81 with attention deficit hyperactivity disorder [ADHD] and 25 with both conditions). DSPD was assessed using the Morningness-Eveningness Questionnaire, followed by a clinical evaluation. Affective temperaments and emotional dysregulation were also investigated through the brief version of the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego and the Reactivity, Intensity, Polarity, Stability questionnaires, respectively. Clinical variables were compared in patients with and without DSPD, and a logistic regression model was used to identify the predictive value of the clinical characteristics on the presence of DSPD. DSPD patients (19% of the total sample) were significantly younger than patients without DSPD, showed an about 4 times higher lifetime history of comorbid ADHD and cyclothymia, and reported higher scores in the irritable and cyclothymic temperamental subscales and in the affective instability and impulsivity dimensions. In the multiple logistic regression, we found a negative predictive value of increasing age on the presence of DSPD, whereas comorbid cyclothymia and ADHD and cyclothymic temperament seem to represent risk factors for DSPD.

A Critical Review of the Psychomotor Agitation Treatment in Youth.

(1) Background: To systematically review evidence on the safety and efficacy of psychopharmacological treatments available for psychomotor agitation (PA) in children and adolescents. (2) Methods: Studies assessing the safety and efficacy of psychopharmacological treatments for acute PA in children and adolescents that were published between January 1984 and June 2022 on PubMed were systematically reviewed. We included: (i) papers that presented a combination of the search terms specified in the "Search strategy" sub-paragraph; (ii) manuscripts in English; (iii) original papers; (iv) prospective or retrospective/observational studies and experimental or quasi-experimental reports. The exclusion criteria were: (i) review papers; (ii) non-original studies including editorials and book reviews; (iii) studies not specifically designed and focused on the selected topic. (3) Results: We selected 42 papers: 11 case series (11/42, 26.19%), 8 chart reviews (8/42, 19.05%), 8 case reports (8/42, 19.05%), 6 double-blind placebo-controlled randomized studies (6/42, 14.29%), 4 double-blind controlled randomized studies (4/42, 9.52%), 4 open-label trials (4/42, 9.52%) and 1 case control (1/42, 2.38%). (4) Conclusions: The drugs most frequently used to treat agitation in children and adolescents were ziprasidone, risperidone, aripiprazole, olanzapine and valproic acid. Further studies are needed to evaluate the efficacy/safety ratio, considering the limited number of observations in this field.

A Case of Delirious Mania Treated with Electroconvulsive Therapy.

(1) Background: Delirious mania is a neuropsychiatric condition characterized by the rapid onset of delirium, psychosis, and mania. Due to the presence of catatonic signs and symptoms, some authors considered this syndrome to be a specific excited catatonia subtype. Usually, delirious mania is responsive to intravenous benzodiazepines (BZDs) or to electroconvulsive therapy (ECT). (2) Methods: In the present study, we describe the case of a 64-year-old woman with a diagnosis of recurrent major depressive disorder. We assessed the severity of the clinical picture and the response to ECT treatment with the Bush-Francis Catatonia Rating Scale (BFCRS). (3) Results: After eleven sessions of ECT, the patient presented a reduced BFCRS total score, with a resolution of the autonomic abnormalities (temperature, respiratory, and heart rate). (4) Conclusions: These data demonstrate how important it is to diagnose this syndrome as soon as possible to set up an effective therapy, avoiding the use of antipsychotic drugs and preventing potentially fatal complications. The initial administration of BZDs IV and the subsequent ECT application, associated with intensive care of life-threatening general medical conditions, guaranteed us a good level of efficacy in obtaining a complete resolution of the clinical picture.

Characteristics of Stress Sensitivity in Heroin Use Disorder Patients during Their Opioid Agonist Treatment.

In the present study, performed on a sample of Heroin Use Disorder (HUD) patients undergoing Opioid Agonist Treatment (OAT), we attempted to explore the relationships between stress sensitivity and heroin addiction-related clinical aspects. HUD patients' stress sensitivity was evaluated with the Heroin/PTSD-Spectrum questionnaire (H/PSTD-S). The Drug Addiction History Questionnaire (DAH-Q), the Symptomatological Check List-90 (SCL-90), and The Behavioural Covariate of Heroin Craving inventory (CRAV-HERO) were all used, as were the Deltito Subjective Wellness Scale (D-SWS), a self-report scale evaluating subjective well-being; the Cocaine Problem Severity Index (CPSI), a questionnaire determining the extent of a cocaine problem; and the Marijuana Craving Questionnaire (MC-Q), an instrument assessing craving for cannabinoids. We checked correlations between stress sensitivity and the extent of HUD clinical features and compared patients with and without problematic stress sensitivity. H/PTSD-S was positively correlated with patients' income, altered mental status, legal problems, the lifetime different treatments index, the current treatment load index, and all SCL-90 indexes and factors. Regarding subjective well-being, stress sensitivity negatively correlated with the contrast best week (last five years) index. Patients with high-stress sensitivity were females with a low income. They exhibited a more severe mental status at treatment entry, greater difficulty in working adaptation, and legal problems during treatment. Additionally, these patients showed a higher level of psychopathology, more impairment in well-being, and more risky behaviours during treatment. Stress sensitivity, as H/PTSD-S, must be considered an outcome of HUD. HUD's addiction history and clinical features are significant risk factors for H/PTSD-S. Therefore, social and behavioural impairment in HUD patients could be considered the clinical expression of the H/PTSD spectrum. In summary, the long-term outcome of HUD is not represented by drug-taking behaviours. Rather, the inability to cope with the contingent environmental conditions is the key feature of such a disorder. H/PTSD-S, therefore, should be seen as a syndrome caused by an acquired inability (increased salience) concerning regular (daily) life events.

High exposure to pharmacological treatments is associated with limited efficacy of electroconvulsive therapy in bipolar depression.

Episode chronicity and medication failure are considered robust predictors of poor response to electroconvulsive therapy (ECT). In this study we explored the associations between indexes of drug exposure during current episode and outcomes of ECT in 168 bipolar depressive patients. The association between response or remission and number of previous pharmacological trials, failure of treatment with antidepressants, antipsychotics or combinations, and sum of maximum Antidepressant Treatment History Form (ATHF) scores obtained in each pharmacological class were tested. 98 patients (58%) were considered responders and 21 remitters (13%). Number of trials, number of adequate trials, ATHF sum, antidepressant-antipsychotic combination therapy failure and failure of two adequate trials were significantly negatively associated with remission. The association with ATHF sum stayed significant when controlling for episode duration and manic symptoms and survived stepwise model selection. No significant associations with response were identified. In conclusion, a history of multiple drug treatments may be linked to a greater resistance to all types of therapies, including ECT. However, we could not exclude that, at least in some patients, a prolonged exposure to pharmacological treatments may be responsible for a greater chronicity and for the presence of residual symptoms, which would explain reduced remission after ECT.

Association of treatment facets, severity of manic symptoms, psychomotor disturbances and psychotic features with response to electroconvulsive therapy in bipolar depression.

OBJECTIVES: Clinically useful predictors of response to electroconvulsive therapy (ECT) are warranted, especially in the case of bipolar depression. The aim of this study was to explore the associations between response and its known and putative correlates. METHODS: Six hundred seventy bipolar depressive patients treated with ECT were included in the study. The association between response (CGI-I ≤ 2) and mean seizure duration, number of treatments, age, sex, bipolar subtype, episode duration, HAM-D and YMRS scores, psychomotor disturbances and psychotic symptoms assessed through BPRS-EV were evaluated by means of univariate and multivariate logistic regression models, including quadratic and/or linear effects of continuous variables. RESULTS: Four hundred eighty three patients (72%) were responders. Among known correlates of response, significant quadratic effects were found for seizure duration and number of treatments, while a linear association was confirmed for episode duration. Among putative correlates, severe motor retardation, tension or agitation, hyperactivity and delusions of guilt were significantly associated with response (p<.01) and a significant quadratic effect was found for YMRS score (p<.01). CONCLUSION: Bipolar depressive patients with severe psychomotor disturbances, mood-congruent delusions and severe mixed features are highly responsive to ECT. A significant improvement in response prediction is expected when considering those clinical characteristics.

Protracted Hiccups Induced by Aripiprazole and Regressed after Administration of Gabapentin.

Hiccups are sudden, repeated, and involuntary contractions of the diaphragm muscle (myoclonic contraction). It involves a reflex arc that, once activated, causes a strong contraction of the diaphragm immediately followed by the closure of the glottis translating into the classic "hic" sound. Hiccups can be short, persistent, and intractable depending on the duration. The most disabling hiccups often represent the epiphenomenon of a medical condition such as gastrointestinal and cardiovascular disorders; central nervous system (CNS) abnormalities; ear, nose, and throat (ENT) conditions or pneumological problems; metabolic/endocrine disorders; infections; and psychogenic disorders. Some drugs, such as aripiprazole, a second-generation antipsychotic, can induce the onset of variable hiccups. We describe herein the cases of three hospitalized patients who developed insistent hiccups after taking aripiprazole and who positively responded to low doses of gabapentin. It is probable that aripiprazole, prescribed at a low dosage (<7.5 mg/day), would act as a dopamine agonist by stimulating D2 and D3 receptors at the "hiccup center" level-located in the brain stem-thus triggering the hiccup. On the other hand, gabapentin led to a complete regression of the hiccup probably by reducing the nerve impulse transmission and modulating the diaphragmatic activity. The present case series suggests the use of low doses of gabapentin as an effective treatment for aripiprazole-induced hiccups. However, our knowledge of the neurotransmitter functioning of the hiccup reflex arc is still limited, and further research is needed to characterize the neurotransmitters involved in hiccups for potential novel therapeutic targets.

The Role of Electroconvulsive Therapy in the Treatment of Severe Bipolar Mixed State.

Electroconvulsive therapy (ECT) results effective in two-thirds of the patients with severe and drug-resistant mixed states. The episode duration is the main predictor of nonresponse. This practice may increase the risk of mood destabilization and chronic complications and may decrease the chance of recovery in many patients. Compared with the burden of neurologic and metabolic side effects associated with long-term use of complex pharmacologic regimens, ECT should be considered a safe option with a very low incidence of severe adverse events and a long-term nondestabilizing effect.

Naturalistic follow-up in bipolar patients after successful electroconvulsive therapy.

BACKGROUND: Electroconvulsive therapy (ECT) is an effective treatment for acute depression, mania and mixed states. We evaluated the long-term outcome of patients with bipolar depression or mixed state, responsive to ECT. METHODS: this observational follow-up study was conducted in 70 patients with Bipolar Disorder: 36 patients met DSM-IV-TR criteria for a major depressive episode (MDE) and 34 for a mixed episode (MXE). During the follow-up after ECT, the relapse rates and the duration of response and remission periods were recorded. RESULTS: the mean duration of the follow-up was 57 weeks. 93% of the patients maintained at least a partial therapeutic response for more than 90% of the follow-up period. 73% of patients fulfilled the criteria for a full remission, 33% showed a depressive relapse and 10% a mixed relapse. No manic relapses occurred but almost 1/3 of the sample presented hypomanic episodes. MDE patients presented higher rates of remission compared to MXE ones. Patients with anxiety disorders reported earlier relapses than those without this comorbidity. Relapsed-patients showed higher functional impairment at baseline evaluation, compared to non-relapsed ones. LIMITATIONS: nonrandom allocation, limited sample size, possible influence of psychopharmacological treatment. CONCLUSIONS: Given several methodological limitations, this study cannot draw definite conclusions but could suggest that in treatment-resistant bipolar patients with severe depression or mixed state, ECT may represent a useful treatment option. Patients with mixed features, comorbid anxiety disorders and higher functional impairment present less favorable outcome. Future research on long-term efficacy of ECT and on clinical predictors of relapse is needed.

Chronobiological dis-rhythmicity is related to emotion dysregulation and suicidality in depressive bipolar II disorder with mixed features.

In Bipolar Disorder, chronobiological rhythm alterations play a key role by negatively influencing its entire trajectory. Our aim was to assess their potential association with emotion dysregulation and suicidality in subjects with Bipolar Disorder. Eighty-five patients with Bipolar Disorder - II depressive episode with mixed features were recruited and 35 as healthy controls. Subjects were evaluated with SCID-DSM-5, the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN), the DERS: Difficulties in Emotion Regulation Scale, the Beck Depression Inventory-II (BDI-II), the Young Mania Rating Scale (YMRS) and the Scale for Suicide Ideation (SSI). When compared to healthy controls, subjects with bipolar disorder showed significantly higher scores in the BRIAN, the DERS, the BDI-II, the YMRS and the SSI total scores. Chronobiological dis-rhythmicity was significantly related to the severity of depressive symptoms, emotion dysregulation, and suicidality in bipolar individuals. In particular, the dis-rythmicity of the sleep/wake pattern showed a significant correlation with manic symptoms, the dis-rythmicity of daily activities with depressive symptoms and emotion dysregulation and that of social life with suicidality. Emotion dysregulation played as a mediator for the association between chronobiological dis-rhythmicity and depressive symptoms (mediated effect = 3.25, p = 0.001) and for social life dis-rhythmicity and suicidality (mediated effect = 2.52, p = 0.011) as well. Therefore, our findings showed that chronobiological dis-rhythmicity in bipolar individuals was related to the severity of mood swings, emotion dysregulation and suicidality. The assessment of potential alteration in chronobiological rhythms should be investigated in the clinical setting in subjects with bipolar disorder to identify those who may benefit from early chronobiological intervention.

Emotional Blunting, Cognitive Impairment, Bone Fractures, and Bleeding as Possible Side Effects of Long-Term Use of SSRIs.

OBJECTIVE: Selective serotonin (5-HT) reuptake inhibitors (SSRIs) are amongst the most prescribed drugs worldwide not only for psychiatric conditions, but also for medical purposes. Converging data gathered throughout the decades following their development would indicate that SSRIs have a broader side effect profile than previously assumed. Therefore, the aim of the present paper was to to review available literature highlighting less common side effects emerging with their long-term use. METHOD: This systematic review, carried out according to PRISMA guidelines, was performed through searching electronic databases of PubMed, Google Scholar, Cochrane Library, Embase, MEDLINE, PsycINFO and Scopus. The keyword used was "SSRIs" combined with the following: "Side effects", or "Emotional blunting or flattening", or "Cognition", or "Neuroimaging", or "Bone", "or "Platelet aggregation", or "Bleeding". RESULTS: The most common side effects, besides the classical ones described in the literature are represented by decreased emotional response to both adversive and pleasurable events, some cognitive impairments, bone fractures and prolonged overall bleeding time. CONCLUSIONS: After analyzing critically the available findings, it should be noted that only the so-called "emotional blunting" is supported by converging data, while results on cognitive impairment are extremely controversial, given some evidence showing that SSRIs may improve cognition. Similarly, no agreement exists on the detrimental effects of SSRIs on bone metabolism and coagulation.Large, prospective and long-term studies are needed to clarify the possible impact of SSRIs on emotions, cognitive functions, bone fractures and coagulation, as well to detect other possible still neglected side effects.

Electroconvulsive therapy and age: Age-related clinical features and effectiveness in treatment resistant major depressive episode.

OBJECTIVE: This study was aimed to compare clinical features, treatments outcomes and tolerability between young (18-45 years), middle age (46-64 years) and old (≥ 65 years) patients treated with bilateral ECT for treatment resistant major depressive episode. METHOD: 402 patients were evaluated 1 day prior to ECT and a week after the treatment termination using the Clinical Global Impression Scale (CGI), the Hamilton Rating Scale for Depression-17 items (HAM-D-17), the Brief Psychiatric Rating Scale (BPRS), the Young Mania Rating Scale (YMRS) and the Mini Mental State Examination (MMSE). Response was defined as a reduction of at least 50% from baseline on the HAM-D-17 score. Remission was defined as a score ≤ 7 on the HAM-D-17 at the final evaluation. RESULTS: Rates of response were not statistically different in the three groups (69.6% in old versus 63.5% in young and 55.5% in middle age groups). No significant differences were also observed in the proportions of remitters between the age groups (31.4% in young group, 27.7% in middle age group and 29.3% in old group). One week after the end of the ECT course the middle and old age groups showed a statistically significant increase in the MMSE score compared to baseline. We did not find significant differences between the three age groups in rates of premature drops-out due to ECT-related side effects. CONCLUSION: Our data support the use of ECT in elderly patients with treatment-resistant major depressive episode, with rates of response around 70% and effectiveness being independent from age. In the old age group the baseline cognitive impairment improved after ECT and no life-threatening adverse event was detected.

Pharmacological Hypotension as a Cause of Delirious Mania in a Patient with Bipolar Disorder.

Delirious mania is a severe but often underrecognized syndrome characterized by rapid onset of delirium, mania, and psychosis, not associated with a prior toxicity, physical illness, or mental disorder. We discuss the case of a delirious mania potentially triggered and maintained by a systemic hypotension induced by antihypertensive drugs. Symptoms recovered completely after the discontinuation of antihypertensive medications and the normalization of blood pressure levels.