Response to electroconvulsive therapy in elderly patients with late-onset bipolar disorder: The impact of cerebral small vessel disease.

OBJECTIVES: Cerebral Small Vessel Disease (CSVD) is a chronic, progressive vascular disorder that confers increased vulnerability to psychiatric syndromes, including late-life mood disorders. In this study, we investigated the impact of CSVD on electroconvulsive therapy (ECT) outcomes in patients with late-onset bipolar disorder (BD). METHODS: A sample of 54 non-demented elderly patients (≥60 years) with late-onset BD and treatment-resistant major depression, mixed state, or catatonia who underwent bilateral ECT were included in this naturalistic observational study. A diagnosis of CSVD was established based on brain neuroimaging performed before ECT. All patients were evaluated before and after ECT using the Brief Psychiatric Rating Scale (BPRS), the Hamilton Rating Scale for Depression (HAM-D), and the Clinical Global Impression scale (CGI). RESULTS: Of the total sample, 19 patients were diagnosed with CSVD (35.2%). No significant differences were observed at baseline between patients with and without CSVD. Overall, a response was obtained in 66%-68.5% of patients, with remission in 56.2%. No significant differences in ECT outcomes were found between those with and without CSVD, and both groups exhibited substantial improvements in symptom severity following ECT. CONCLUSIONS: The outcome of ECT in late-onset BD was not influenced by the presence of CSVD. This finding aligns with previous research on unipolar depression. Accordingly, ECT should be considered for elderly patients with late-onset BD, regardless of the presence of CSVD.

Pseudodementia in Patients with Unipolar and Bipolar Disorders: A Case Series and Literature Review.

Even though pseudodementia has been historically linked to depression, other psychiatric conditions may cause reversible cognitive alterations. The purpose of this study is to improve our understanding of pseudodementia occurring throughout the entire bipolar spectrum. A systematic review was conducted according to PRISMA guidelines. PubMed, Scopus, and Web of Science databases were searched up to March 2023. Fifteen articles on patients with pseudodementia and bipolar disorder (BD), mania, hypomania, or mixed depression have been included. Moreover, seven female patients with mood disorders diagnosed with pseudodementia have been described. According to our research, pseudodementia in patients with BD mostly occurs during a depressive episode. However, pseudodementia has also been observed in the context of manic and mixed states. Psychomotor and psychotic symptoms were commonly associated. The most typical cognitive impairments were disorientation, inattention, and short-term memory deficits. Alterations in neuroimaging were frequently observed. Electroconvulsive therapy and lithium, either alone or in combination with antipsychotics, resulted in the most widely used therapies. Cognitive decline may occur in a substantial proportion of patients. Since pseudodementia can manifest along the entire mood spectrum, it should be taken into consideration as a possible diagnosis in BD patients showing cognitive deficits during manic, mixed, and depressive states.

The impact of mild behavioral impairment on the prognosis of geriatric depression: preliminary results.

Our study aimed to examine how the presence of Mild Behavioral Impairment (MBI) symptoms influenced the outcome of late-life depression (LLD). Twenty-nine elderly (≥ 60 years) depressive patients, including eleven (37.9%) with MBI, were recruited and followed-up on average for 33.41 ±â€…8.24 weeks. Psychiatric symptoms severity and global functioning were assessed, respectively, using the Brief Psychiatric Rating Scale (BPRS) and the Global Assessment of Functioning (GAF) scale. BPRS total score significantly decreased from baseline to follow-up (P < 0.001, d = 1.33). The presence of MBI had no significant effect on mood and cognitive symptoms improvement. On the contrary, while a significant increase in GAF score was observed in patients without MBI (P = 0.001, d = 1.01), no significant improvement of global functioning was detected in those with MBI (P = 0.154, d = 0.34) after 6-month follow-up. The presence of MBI in patients with LLD may negatively affect long-term outcome, slowing or preventing functional improvement.

Type 2 diabetes mellitus is associated with manic morbidity in elderly patients with mood disorders.

The association between mood disorders, especially bipolar disorder (BD), and metabolic disorders, is long known. However, to which extent metabolic disorders affect the course of mood disorders in late life is still open to inquiring. To assess the impact of type 2 diabetes mellitus (T2DM) on late-life mood disorders a retrospective chart review was performed. Elderly depressive patients (≥ 65 years) diagnosed with Major Depressive Disorder (N = 57) or BD (N = 43) and followed up for at least 18 months were included and subdivided according to the presence of T2DM comorbidity. Vascular encephalopathy (39.1% vs. 15.6%, P  = 0.021) and neurocognitive disorders (21.7% vs. 5.2%, P  = 0.028), were more frequently reported in patients with T2DM than in those without. Patients with T2DM showed a greater percentage of follow-up time in manic episodes (r = -0.23, P  = 0.020) and a higher rate of manic episode(s) during follow-up (21.7% vs. 5.2%, P  = 0.028) than those without. When restricting longitudinal analyses to patients with bipolar spectrum disorders, results were confirmed. In line with the well-known connection between BD and metabolic disorders, our data support an association between T2DM and unfavorable course of illness in the elderly with BD.

Mild Behavioral Impairment in Psychogeriatric Patients: Clinical Features and Psychopathology Severity.

The Mild Behavioral Impairment (MBI) concept was developed to determine whether late-onset persistent neuropsychiatric symptoms (NPSs) may be early manifestations of cognitive decline. Our study aims to investigate the prevalence and differentiating features of MBI with respect to major neurocognitive disorders (MNDs) and primary psychiatric disorders (PPDs). A total of 144 elderly patients who were referred to our psychogeriatric outpatient service were recruited. The severity of mental illness was evaluated by means of the Clinical Global Impression Severity scale, the severity of psychopathology was evaluated by means of the Brief Psychiatric Rating Scale (BPRS), and overall functioning was evaluated by means of the Global Assessment of Functioning scale. The sample included 73 (50.6%) patients with PPDs, 40 (27.8%) patients with MBI, and 31 (21.5%) patients with MNDs. Patients with MNDs reported the greatest severity of mental illness, the highest BPRS Total, Psychosis, Activation, and Negative Symptom scores, and the lowest functioning. Patients with MBI and PPDs had comparable levels of severity of mental illness and overall functioning, but MBI patients reported higher BPRS Total and Negative Symptom scores than PPD patients. Patients with MBI frequently reported specific clinical features, including a higher severity of apathy and motor retardation. These features merit further investigation since they may help the differential diagnosis between MBI and PPDs.

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.

Occurrence of involuntary movements after prolonged misuse of zolpidem: a case report.

Zolpidem is a non-benzodiazepine agent used for short-term treatment of insomnia. Several cases of dependence and withdrawal from zolpidem are reported in the literature. Furthermore, involuntary movements after prolonged zolpidem misuse have been described. In this case report, a 69-year-old Italian woman with no history of diagnosed psychiatric or neurologic diseases developed uncontrolled movements and a depressive-anxious syndrome after twelve-year zolpidem misuse. The underlying mechanisms of involuntary movements occurring after long-term zolpidem intake are unknown; yet, we suggest that zolpidem might induce an increase in dopamine release through inhibition of gamma-aminobutyric acid neurons tonically suppressing dopamine cells. Future studies on the occurrence of persistent disorders after long-term benzodiazepine or Z-drug abuse are needed and clinicians should pay attention to the risk of tardive syndromes related to zolpidem misuse, especially in the case of long-term intake of over-therapeutic dosages.

Bipolar Disorder and Manic-Like Symptoms in Alzheimer's, Vascular and Frontotemporal Dementia: A Systematic Review.

BACKGROUND: An increased risk of manic episodes has been reported in patients with neurodegenerative disorders, but the clinical features of bipolar disorder (BD) in different subtypes of dementia have not been thoroughly investigated. OBJECTIVES: The main aim of this study is to systematically review clinical and therapeutic evidence about manic syndromes in patients with Alzheimer's disease (AD), vascular dementia (VaD), and frontotemporal dementia (FTD). Since manic-mixed episodes have been associated to negative outcomes in patients with dementia and often require medical intervention, we also critically summarized selected studies with relevance for the treatment of mania in patients with cognitive decline. METHODS: A systematic review of the literature was conducted according to PRISMA guidelines. PubMed, Scopus, and Web of Science databases were searched up to February 2022. Sixty-one articles on patients with AD, VaD, or FTD and BD or (hypo) mania have been included. RESULTS: Manic symptoms seem to be associated to disease progression in AD, have a greatly variable temporal relationship with cognitive decline in VaD, and frequently coincide with or precede cognitive impairment in FTD. Overall, mood stabilizers, and electroconvulsive therapy may be the most effective treatments, while the benefits of short-term treatment with antipsychotic agents must be balanced with the associated risks. Importantly, low-dose lithium salts may exert neuroprotective activity in patients with AD. CONCLUSION: Prevalence, course, and characteristics of manic syndromes in patients with dementia may be differentially affected by the nature of the underlying neurodegenerative conditions.

Psychiatric Symptoms in Patients with Cerebral Endometriosis: A Case Report and Literature Review.

Endometriosis is a systemic medical condition characterized by endometrial tissue that is abnormally implanted in extrauterine sites, including the central nervous system. In this article, we reported the case of a patient with presumed cerebral endometriosis who was diagnosed with bipolar disorder and panic disorder and systematically reviewed the literature for previously reported neuropsychiatric symptoms in patients with cerebral and cerebellar endometriosis. The PubMed, Scopus, and Web of Science bibliographic databases were searched according to the PRISMA guidelines. Seven previous case reports were found and described. While neurological disturbances dominated the clinical picture in the cases retrieved from the literature, our patient represented the first case to show both neurological and psychiatric manifestations. Atypical features of bipolar disorder including chronic mood instability, mixed episodes, and excitatory interepisodic symptoms were highlighted. During the neuropsychological evaluation, a dysexecutive profile consistent with frontal lobe pathology was evidenced. We hypothesized that the course and features of the illness were largely influenced by the presence of documented brain lesions compatible with endometrial implants, especially in the frontal region. Accordingly, patients with endometriosis who exhibit neurological as well as mental symptoms should be investigated for cerebral lesions.

Risk of conversion to bipolar disorder in patients with late-onset major depression.

To evaluate the impact of age at onset on late-life depression course and on risk of conversion to bipolar disorder (BD). A retrospective chart review of 100 elderly patients (age ≥ 65 years) diagnosed with a moderate-to-severe depressive episode and followed up for at least 18 months was conducted. Among patients affected by major depressive disorder ( N = 57), follow-up morbidity differences between those with typical onset depression (TOD) (<60 years) and those with late-onset depression (LOD) (≥60 years) were investigated using Wilcoxon rank-sum test and Cox proportional hazard model. Patients belonging to the LOD group had a significantly lower percentage of follow-up time spent with depressive symptoms compared with patients with TOD ( r = 0.36; P = 0.006), but significantly more time spent with (hypo)manic episodes ( r = -0.31; P = 0.021). Moreover, LOD was significantly associated with a faster conversion to BD (hazard ratio = 3.05; P = 0.037). Depression first emerging in late life may represent an unstable condition with a high risk to convert to BD. Given the potential clinical implications, further studies on the course of LOD are required.

Bipolar Spectrum disorders in Parkinson's disease: a systematic evaluation.

OBJECTIVE: Psychiatric disorders are very common in patients affected by Parkinson's disease (PD). However, comorbidity with Bipolar Spectrum disorders is understudied. The aim of this study is to explore the clinical correlates of PD associated with Bipolar Spectrum disorders. METHODS: One hundred PD patients were screened for psychiatric comorbidities, cognitive profile, motor, and non-motor symptoms. The sample was divided into three groups: PD-patients with Bipolar Spectrum disorders (bipolar disorder type I, type II, and spontaneous or induced hypomania; N = 32), PD-patients with others psychiatric comorbidities (N = 39), PD-patients without psychiatric comorbidities (N = 29). Clinical features were compared among the groups using analysis of variance and chi-square test. A logistic regression was performed to evaluate the association between Bipolar Spectrum disorders and early onset of PD (≤50 years) controlling for lifetime antipsychotic use. RESULTS: In comparison with PD patients with and without other psychiatric comorbidity, subjects affected by Bipolar Spectrum disorders were younger, showed more frequently an early onset PD, reported more involuntary movements and a higher rate of impulse control disorders and compulsive behaviors. No differences were observed in indexes of exposure to dopamine agonist treatments. The early onset of PD was predicted by Bipolar Spectrum comorbidity, independently from lifetime antipsychotic use. CONCLUSION: Bipolar Spectrum disorders are common in early onset PD. The presence of bipolar comorbidity could identify a particular subtype of PD, showing higher rates of neurological and psychiatric complications and deserving further investigation.

Prevalence and Clinical Correlates of Comorbid Anxiety and Panic Disorders in Patients with Parkinson's Disease.

Mood and anxiety disorders are the most common neuropsychiatric syndromes associated with Parkinson's disease (PD). The aim of our study was to estimate the prevalence of lifetime and current anxiety disorders in patients with Parkinson's Disease (PD), to explore possible distinctive neurological and psychiatric features associated with such comorbidity. One hundred patients were consecutively recruited at the Movement Disorders Section of the Neurological Outpatient Clinic of the University of Pisa. According to the MINI-Plus 5.0.0, 41 subjects were diagnosed with lifetime anxiety disorder (22 with panic disorder) and 26 were diagnosed with current anxiety disorders. Patients with anxiety disorders were more frequently characterized by psychiatric symptoms preceding PD, lifetime major depression and antidepressant treatments. They showed more anxious temperamental traits and scored higher at Parkinson Anxiety Scale (PAS) and persistent anxiety subscale. Current anxiety disorders were associated with more severe psychopathology, depressive symptomatology, and avoidant behavior. Among anxiety subtypes, patients with lifetime panic disorder showed higher rates of psychiatric symptoms before PD, lifetime unipolar depression, current psychiatric treatment, and a more severe psychopathology. Given the overall high impact of anxiety on patients' quality of life, clinicians should not underestimate the extent of different anxiety dimensions in PD.

Plasma redox and inflammatory patterns during major depressive episodes: a cross-sectional investigation in elderly patients with mood disorders.

BACKGROUND: While both depression and aging have been associated with oxidative stress and impaired immune response, little is known about redox patterns in elderly depressed subjects. This study investigates the relationship between redox/inflammatory patterns and depression in a sample of elderly adults. METHODS: The plasma levels of the advanced products of protein oxidation (AOPP), catalase (CAT), ferric reducing antioxidant power (FRAP), glutathione transferase (GST), interleukin 6 (IL-6), superoxide dismutase (SOD), total thiols (TT), and uric acid (UA) were evaluated in 30 patients with mood disorders with a current depressive episode (depressed patients, DP) as well as in 30 healthy controls (HC) aged 65 years and over. Subjects were assessed with the Hamilton Depression Rating Scale (HAM-D), the Hamilton Rating Scale for Anxiety (HAM-A), the Geriatric Depression Rating Scale (GDS), the Scale for Suicide Ideation (SSI), the Reason for Living Inventory (RFL), the Activities of Daily Living (ADL), and the Instrumental Activity of Daily Living (IADL). RESULTS: DP showed higher levels than HC of AOPP and IL-6, while displaying lower levels of FRAP, TT, and CAT. In the DP group, specific correlations were found among biochemical parameters. SOD, FRAP, UA, and TT levels were also significantly related to psychometric scale scores. CONCLUSION: Specific alterations of redox systems are detectable among elderly DP.

Mild Behavioral Impairment: presentation of the diagnostic criteria and the Italian version of the MBI-Checklist.

Neuropsychiatric symptoms (NPS) are common in the prodromal stage of dementia and can precede the onset of cognitive impairment. The presence of NPS in cognitively normal patients or in patients with Mild Cognitive Impairment (MCI) is associated with an increased risk of progression along the neurodegenerative process. The need to identify, in the early stages of the disease, the population at risk of cognitive decline has led to the formulation of the concept of Mild Behavioral Impairment (MBI). This neurobehavioral syndrome is characterized by late-onset sustained psychiatric symptoms, in patients without cognitive deficits or in those with MCI, identifying a condition associated with an increased probability of conversion into dementia. MBI represents the neurobehavioral axis of pre-dementia risk states, as a complement to the neurocognitive axis of MCI. For some, MBI may be the initial manifestation of neurodegenerative disease, observed before cognitive impairment is apparent. The Mild Behavioral Impairment-Checklist (MBI-C) was developed on the basis of the MBI diagnostic criteria, established by the International Society to Advance Alzheimer's Research and Treatment (ISTAART). The MBI-C allows to identify, in a standardized way, patients with MBI and to follow the course of their neurodegenerative disease. This article describes the creation of the MBI-C scale and presents its Italian version.

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.

[Treatment-resistant depression: state of the art. Part I. Nosography and clinic]. / Depressione resistente al trattamento: stato dell'arte. Parte I. Nosografia e clinica.

AIMS: This work would give an overall vision of the actual knowledge about nosography and clinic of treatment-resistant depression. METHOD: A PubMed, PsychInfo, Google Scolar search was done using the key words "resistant depression", "STAR*D", "bipolar depression", "staging". Have been selected exclusively works in English, French and Italian languages. RESULTS: Treatment-resistant depression is one of the most important problem in public health. Nevertheless a general consensus about its definition and staging does not exist at now. Principal risk factors and associated comorbidities are well known including the association with bipolar spectrum; anyway the disease particularly common among depressed outpatients is still very disabling, responsible of an often chronic course, with numerous relapses and high risk of suicide. DISCUSSION AND CONCLUSION: The future investigations, once improved procedures for differential diagnosis and subtyping of clinical depression, should be directed to the search of a shared definition of treatment resistance and the development of specific therapeutic protocols.

Ziprasidone as adjunctive therapy in severe bipolar patients treated with clozapine.

Aim. To confirm the efficacy and tolerability of ziprasidone as adjunctive therapy in bipolar patients partially responding to clozapine or with persisting negative symptoms, overweight, or with metabolic syndrome. Methods. Eight patients with psychotic bipolar disorder were tested with the BPRS, the HAM-D, and the CGI at T0 and retested after 2 weeks (T1). Plasma clozapine and norclozapine levels and BMI were tested at T0 and T1. Results. Ziprasidone was well tolerated by all the patients. BPRS and HAM-D scores were reduced in all patients. BMI was reduced in patients with a BMI at T0 higher than 25. Plasma levels of clozapine and norclozapine showed an irregular course.

[Treatment-resistant depression: state of the art Part II. Treatment]. / Depressione resistente al trattamento: stato dell'arte Parte II. Trattamento.

AIM: This work would give an overall and up-to-date vision of psychopharmacological and physical strategies of treatment for resistant depression. METHOD: A PubMed search was done using the keywords "resistant depression treatment", "electroconvulsive therapy", "antidepressants", and the inclusion criteria of adult samples, English, French or Italian languages. RESULTS: Lots of psycho-pharmacological and physical treatment strategies for resistant depression exist; anyway there is no consensus about their indications and efficacy, which appears still unsatisfactory. DISCUSSION AND CONCLUSION: Further research should move towards the identification of specific clinical picture of treatment resistant depression to develop more efficacious and selective treatment protocols.

Catatonia and neuroleptic malignant syndrome: two disorders on a same spectrum? Four case reports.

We present the history of four bipolar patients who developed neuroleptic malignant syndrome (NMS) after antipsychotic treatment, focusing on the relationship between NMS and catatonia. In all cases, the administration of antipsychotics has been suspended as soon as fever and autonomic disturbances occurred. A supportive therapy was initiated to stabilize general conditions, then every patient started electroconvulsive therapy (ECT) in combination with benzodiazepines (BDZ). The risk of complications was reduced by the quick adoption of supportive care, whereas the combination of ECT and BDZ was effective in resolving the clinical picture. These cases may provide further support to the hypothesis that catatonia and NMS are disorders pertaining to the same spectrum of illness because the onset or exacerbation of catatonic symptoms coincided with the administration of antipsychotics. Our experience confirms the efficacy and safety of ECT in combination with BDZ as treatment of NMS and residual catatonia.

[Catatonia and neuroleptic malignant syndrome: two disorders on a same spectrum? Three case reports]. / Catatonia e sindrome maligna da neurolettici: condizioni cliniche diverse di uno stesso spettro? Descrizione di tre casi.

AIM: The authors present the cases of three bipolar patients who developed Neuroleptic Malignant Syndrome (NMS) after antipsychotic treatment, both typical and atypical, focusing on relationship between NMS and catatonia. METHODS: In all three cases, administration of antipsychotics has been stopped at once, when fever and autonomic disturbances occurred. A supportive therapy (including rehydration, electrolyte restoration and blood pressure aids, together with antipyretics, antibiotics and anticoagulants) was prescribed in order to stabilize general conditions. Every patient started then Electroconvulsive Therapy (ECT) in combination with benzodiazepines. RESULTS: High risk of complications and lethal outcome, associated with NMS, were successfully reduced by the tempestive adoption of a supportive care, while combination between ECT and BDZ was effective in resolution of clinical picture. DISCUSSIONS; These cases may provide further evidences about hypothesis of catatonia and NMS as disorders on the same spectrum. In one patient, NMS occurred overlapping with a previous catatonic state, while two others exhibited catatonic features after resolution of NMS. However, catatonic symptoms arose or worsened with administration of antipsychotics, supporting hypothesis of neuroleptic-induced catatonia as a step of progressive development of NMS. Our experience also confirms efficacy and safety of ECT in combination with BDZ as treatment of NMS and residual catatonia.