Episodic Visual Learning/Memory and Attentional Flexibility in Patients With Major Depressive Disorder After Clinically Effective Electroconvulsive Therapy.

OBJECTIVES: This study is a follow-up of a previous one reporting that the neuropsychological profile of pharmacoresistant patients with major depressive disorder referred for electroconvulsive therapy (ECT, ECT group) contrasted with that of their pharmacorespondent counterparts (NECT group). The NECT group exhibited severe visuospatial memory and minor executive deficits; the ECT group presented the reverse pattern. In that same ECT group, the current follow-up study examined the effects of clinically effective ECT on both cognitive domains 2 months later. METHODS: Fifteen ECT patients were administered Hamilton Depression (HAMD-24), Hamilton Anxiety (HAMA), Mini-Mental State Examination Scales and 5 tests of Cambridge Neuropsychological Test Automated Battery at intake (pre-ECT), end of ECT course (post-ECT), and 2 months thereafter (follow-up). RESULTS: Electroconvulsive therapy was effective in relieving clinical depression. After a post-ECT decline, the patients exhibited significant improvement in both Cambridge Neuropsychological Test Automated Battery, paired associate learning, and Stockings of Cambridge. By contrast, their major pre-ECT deficit in intra/extradimensional set shifting remained virtually unaffected. CONCLUSIONS: Our findings suggest that attentional flexibility deficits may constitute a neuropsychological trait-like feature of pharmacoresistant, ECT-referred major depressive disorder patients. However, this deficit does not seem generalized, given patient improvement in episodic visual learning/memory and some indication of improvement in spatial planning after ECT.

Baseline heartbeat perception accuracy and short-term outcome of brief cognitive-behaviour therapy for panic disorder with agoraphobia.

BACKGROUND: Increased heartbeat perception accuracy (HBP-accuracy) may contribute to the pathogenesis of Panic Disorder (PD) without or with Agoraphobia (PDA). Extant research suggests that HBP-accuracy is a rather stable individual characteristic, moreover predictive of worse long-term outcome in PD/PDA patients. However, it remains still unexplored whether HBP-accuracy adversely affects patients' short-term outcome after structured cognitive behaviour therapy (CBT) for PD/PDA. AIM: To explore the potential association between HBP-accuracy and the short-term outcome of a structured brief-CBT for the acute treatment of PDA. METHOD: We assessed baseline HBP-accuracy using the "mental tracking" paradigm in 25 consecutive medication-free, CBT-naive PDA patients. Patients then underwent a structured, protocol-based, 8-session CBT by the same therapist. Outcome measures included the number of panic attacks during the past week, the Agoraphobic Cognitions Questionnaire (ACQ), and the Mobility Inventory-Alone subscale (MI-alone). RESULTS: No association emerged between baseline HBP-accuracy and posttreatment changes concerning number of panic attacks. Moreover, higher baseline HBP-accuracy was associated with significantly larger reductions in the scores of the ACQ and the MI-alone scales. CONCLUSION: Our results suggest that in PDA patients undergoing structured brief-CBT for the acute treatment of their symptoms, higher baseline HBP-accuracy is not associated with worse short-term outcome concerning panic attacks. Furthermore, higher baseline HBP-accuracy may be associated with enhanced therapeutic gains in agoraphobic cognitions and behaviours.

Psychotic major depression in older people: a systematic review.

OBJECTIVE: This study aimed to systematically review available evidence relevant to the following issues: (1) whether psychotic major depression (PMD) in older people differs in overall severity from non-PMD, besides the presence of psychotic symptoms; (2) whether it constitutes a distinct clinical entity from non-PMD; and (3) whether it differs from PMD in younger adults. DESIGN: A computerized MEDLINE, PsycINFO and the entire Cochrane Library search has been performed in June 2013 for prospective controlled studies investigating PMD features in older people. RESULTS: Thirty-five relevant studies were identified. PMD in older people compared with non-PMD has been shown to present with overall more severe depressive symptomatology, more psychomotor disturbance, more guilt feelings, more depressive episodes with psychosis, worse prognosis, more severe executive dysfunction associated with frontal lobe atrophy, and lower serum dopamine ß-hydroxylase activity. No differences in the efficacy of an antidepressant plus antipsychotic combination versus antidepressant monotherapy in the acute treatment as well as in the maintenance treatment were found. PMD in older patients is characterized by more somatic complaints and delusions of hypochondriacaland impending disaster content and by a lower comorbidity with anxiety disorders compared with PMD in younger adults. CONCLUSIONS: Psychotic major depression in older people is associated with higher severity in most clinically important key features than in non-PMD. However, available evidence is still insufficient for the conclusive elucidation of its nosological status. Finally, the differences between PMD in older and younger patients can be attributed to biological and psychosocial changes of old age.

Cognitive effects of pregabalin in the treatment of long-term benzodiazepine-use and dependence.

OBJECTIVE: Long-term benzodiazepine (BDZ) use and dependence affect cognitive functioning adversely and partly irreversibly. Emerging evidence suggests that pregabalin (PGB) might be a safe and efficacious treatment of long-term BDZ use. The aim of the present study was to investigate the changes in several core cognitive functions after successful treatment of long-term BDZ use and dependence with PGB. METHODS: Fourteen patients with long-term BDZ use (mean duration >15 years) underwent neuropsychological assessment with the mini-mental state examination and four tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) battery before the initiation of PGB treatment and at a two months follow-up after the cessation of BDZs. Patients' CANTAB percentile score distributions were compared with normative CANTAB data. RESULTS: Patients improved on cognitive measures of global cognitive functioning, time orientation, psychomotor speed, and visuospatial memory and learning with strong effect sizes. By contrast, they failed to improve on measures of attentional flexibility. Despite their significant improvement, patients' scores on most tests remained still at the lower percentiles of CANTAB normative scores. CONCLUSIONS: Although preliminary, our findings suggest that successful treatment of long-term BDZ use with PGB is associated with a substantial, though only partial, recovery of BDZ-compromised neuropsychological functioning, at least at a 2-month follow-up.

Can cognitive deficits differentiate between schizophrenia with and without obsessive-compulsive symptoms?

BACKGROUND: The frequent occurrence of obsessive-compulsive symptoms (OCS) in the course of schizophrenia and their impact on the functional outcome of the illness underlie the suggestion that the presence of OCS represents a separate subtype of schizophrenia, with a distinct clinical presentation and prognosis and specific neurobiological characteristics. This study investigated whether the presence of OCS in schizophrenia is associated with worse cognitive functioning in the domains of processing speed, executive functions and visuospatial memory. We also explored whether the degree of impairment in any of these cognitive domains could predict group membership (i.e. Schizophrenia with OCS [Sch-OCS] and Schizophrenia without OCS) and if there was a relationship between cognitive functioning and severity of OCS within the Sch-OCS group. METHODS: Forty patients with schizophrenia, 20 with and 20 without OCS, individually matched for age, gender, years of education and severity of psychotic symptoms and 20 healthy controls underwent a comprehensive neuropsychological assessment. RESULTS: Only lower performance in processing speed discriminated patients with OCS from patients without OCS. Processing speed impairment not only classified patients in OCS or non-OCS group but was also independent of the severity of OCS symptoms. CONCLUSIONS: The notion of additive effects of both schizophrenia and OCD on the structural and functional integrity of the brain circuits that support cognitive functions warrants further investigation in longitudinal neuropsychological and neuroimaging studies with larger samples and sufficient variation in the severity of OCS.

Testosterone and dehydroepiandrosterone sulfate in female anxious and non-anxious major depression.

OBJECTIVES: Major Depression with severe anxiety has been proposed as a distinct clinical variant of Major Depressive Disorder (MDD). This proposal invites the investigation of the differential biological correlates of the anxious versus non-anxious MDD. One such research area might be their possible differential associations with androgens. METHODS: Plasma total testosterone and dehydroepiandrosterone were assessed in adequately matched female inpatients with anxious MDD, non-anxious MDD and normal controls. RESULTS: Androgen levels were significantly lower in both patient groups compared to those of controls. Moreover, they were significantly lower in anxious MDD patients compared to those of their non-anxious MDD counterparts. The limitations of this study were cross-sectional design of the study, the small sample size of the study sample and the outpatient status of the control group. In addition, free testosterone levels were not measured. CONCLUSIONS: Our findings indicate that female major depression is associated with lower androgen levels, a deficiency aggravated by the severity of their concomitant anxiety.

On the differential diagnosis of anxious from nonanxious major depression by means of the Hamilton Scales.

OBJECTIVE: Anxious major depressive disorder (A-MDD) is differentially diagnosed from nonanxious MDD (NA-MDD) as MDD with a cut-off score ≥ 7 on the HAM-D anxiety-somatization factor (ASF). We investigated whether additional HAM-D items discriminate A-MDD from NA-MDD. Moreover, we tested the validity of ASF criterion against HAM-A, gold standard of anxiety severity assessment. METHODS: 164 consecutive female middle-aged inpatients, diagnosed as A-MDD (n = 92) or NA-MDD (n = 72) by the normative HAM-A score for moderate-to-severe anxiety (≥ 25), were compared regarding 17-item HAM-D scores. The validity of ASF ≥ 7 criterion was assessed by receiver-operating characteristics (ROC) analysis. RESULTS: We found medium and large effect size differences between A-MDD and NA-MDD patients in only four out of the six ASF items, as well as in three further HAM-D items, namely, those of agitation, middle insomnia, and delayed insomnia. Furthermore, the ASF cut-off score ≥ 9 provided the optimal trade-off between sensitivity and specificity for the differential diagnosis between A-MDD and NA-MDD. CONCLUSION: Additional HAM-D items, beyond those of ASF, discriminate A-MDD from NA-MDD. The ASF ≥ 7 criterion inflates false positives. A cut-off point ≥ 9 provides the best trade-off between sensitivity and specificity of the ASF criterion, at least in female middle-aged inpatients.

Corrected QT interval changes during electroconvulsive therapy-antidepressants-atypical antipsychotics coadministration: safety issues.

Both old and newer antidepressants and some atypical antipsychotics, such as ziprasidone and quetiapine, used as augmentation agents in severe major depression, are known to increase corrected QT (QTc) interval. We investigated the safety of the coadministration of electroconvulsive therapy with an antidepressant-ziprasidone-quetiapine combination with respect to QTc interval in 6 female patients with severe major depression resistant to pharmacotherapy alone. Each patient underwent a series of 10 to 11 sessions of bilateral electroconvulsive therapy. Corrected QT intervals were calculated at baseline and several times up to 10 minutes after seizure cessation. Overall, QTc interval changes remained within normal limits, without the occurrence of any cardiac adverse events. Our findings suggest that the coadministration of these treatments might be safe, at least with respect to QTc interval changes.

Safety of the electroconvulsive therapy-ziprasidone combination.

In clinical practice, a nonnegligible proportion of patients with mood or psychotic disorders undergo electroconvulsive therapy (ECT) concomitantly with pharmacotherapy. Ziprasidone, a combined serotonin and dopamine receptor antagonist, is a second-generation antipsychotic agent with a lower incidence of extrapyramidal motor symptoms and prolactin elevation and a safer profile of adverse effects on plasma lipids, glucose levels, and body weight than other antipsychotics. To the best of our knowledge, there are as yet no available reports on the safety of the ECT-ziprasidone combination. We report here on a series of 8 female inpatients who underwent ECT while receiving ziprasidone (20-80 mg/d) as part of their regimen. Seven patients were treated for major depressive episode in the context of unipolar major depressive disorder (n = 5) or of bipolar disorder I (n = 2), whereas 1 patient was treated for exacerbation of schizophrenic symptoms. In all cases, the combination was well tolerated with only minimal adverse effects and unremarkable changes in corrected QT interval.

Caffeine challenge and breath-holding duration in patients with panic disorder.

OBJECTIVE: Breath-holding (BH) has been used as a simple probe to increase endogenous carbon dioxide (CO2). In patients with Panic Disorder (PD), lower baseline BH duration is associated with caffeine-induced panic attacks. In this paper, we assessed BH duration in PD patients in relation to panic attacks induced by caffeine intake. METHODS: BH duration and state anxiety were assessed in 40 PD patients (12 males), both at baseline and after a 400-mg caffeine challenge test. RESULTS: Patients panicking after caffeine administration (14 patients, 4 males) exhibited a significant reduction of their post-challenge BH duration, while no change of the BH duration was observed in non-panicking patients (26 patients, 8 males). Reduction in post-challenge BH duration was not related to higher anxiety levels--as reflected in the State-Trait Anxiety Inventory-State Form scores--independently of the occurrence of a panic attack. Panickers exhibited significantly lower baseline BH duration, compared to non-panickers. CONCLUSIONS: Our findings indicate that in PD patients, caffeine-induced panic attacks are strongly associated with a significant reduction of BH duration at both pre- and post-challenge. Jointly, these findings suggest that in a subgroup of PD patients, sensitivity to endogenous CO2 accumulation may underlie both the lower BH durations and the caffeine-induced panic attacks. In this subgroup of PD patients, caffeine might exert its panicogenic properties through the exacerbation of patients' already pathological hypersensitivity to CO2 accumulation, as indicated by both the significant decrease of their BH duration at post-challenge and by their significantly lower baseline BH duration respectively.

Dimensional approach to delusions in psychotic depression in the elderly: factor structure and clinical correlates.

OBJECTIVE: The present study attempted to investigate the clinically important broader dimensions of clinical characteristics of delusions, through multivariate analysis, in a pure sample of elderly unipolar delusional depressives as well as to test their external validity against a set of demographic, anamnestic and psychopathological validators. METHODS: Fifty inpatients suffering from psychotic major depression (PMD) in the context of major depressive disorder, 60 years old or older, were assessed on the basis of SCID IV, HRSD, MMSE and by three-point ordinal scales of 12 clinical, intrinsic or relational characteristics of delusions tested for their inter-rater reliability. RESULTS: Principal Component Analysis resulted in the extraction of five factors, jointly accounting for 69.7% of the total variance. The five factors were interpreted as representing the dimensions of delusional strength, acute upsetting, delusional organization, incomprehensibility and incitation to actions. Most of the factors were differentially associated with patients' demographic, anamnestic and clinical variables. CONCLUSION: Our results overlap in part with those of another similar study in delusional depressives of all age-ranges, differing, however, in respects possibly attributable to peculiarities of elderly depressives. Overall, the findings of the present study contribute to the further elucidation of major clinical dimensions of delusions in PMD in the elderly and the testing of their external validity.

Pregabalin in the discontinuation of long-term benzodiazepine use: a case-series.

Tolerance, dependence, and adverse effects on cognitive functions are well known consequences of long-term use of benzodiazepines (BDZ), especially at high doses; this raises thorny therapeutic problems in their discontinuation. One promising pharmacological agent in BDZ discontinuation might be the newer antiepileptic, pregabalin (PGB), which has already successfully been tested in the treatment of anxiety disorders. We report on a series of four women with long-term, high-dose dependence on BDZ, who were treated with PGB at doses of 225-600 mg. All four patients discontinued BDZ successfully in 3-7 weeks. Moreover, they had an impressive reduction of their previous anxiety levels under BDZ. In addition, the patients showed a clinically significant amelioration in their cognitive functioning. The side effects of PGB were mild and transient, persisting only during the first 2 weeks of treatment. Although our findings are preliminary, they suggest that PGB might be one of the most promising of the newer agents in the treatment of BDZ dependence.

Levetiracetam in the treatment of antipsychotics-resistant Tourette syndrome.

Levetiracetam, an anti-epileptic agent that enhances GABAergic neurotransmission, is one of the newest alternative treatments of Tourette syndrome (TS). We present the case of a 23-year-old female patient suffering from TS since the age of 7, who exhibited poor response to a variety of agents (haloperidol, pimozide, clonidine and various adjunctive agents) and had four hospitalizations during the previous 2 years due to the deterioration of her clinical state. On her last admission, in addition to clonidine 600 microg/day (already part of her regimen for the previous 4 years), levetiracetam was prescribed, up to 2000 mg/day, progressively titrated over a 3-week period. The patient presented a significant improvement on her TS symptomatology (the score on the Yale Global Tic Severity Scale dropped from 70 at admission, to 25 five weeks later, at discharge), which was preserved during the subsequent 4 months, without any serious side-effect.

Pregabalin in the discontinuation of long-term benzodiazepines' use.

OBJECTIVE: Tolerance, dependence, and adverse effects on cognitive functions are well-known consequences of long-term use of benzodiazepines (BDZ), especially at high doses, raising thorny therapeutic problems in their discontinuation. One promising pharmacological agent in BDZ discontinuation might be the newer anti-epileptic pregabalin, already successfully tested in the treatment of anxiety disorders. METHODS: We report on a sample of 15 patients with long-term, mostly high-dose dependence from BDZ, treated with pregabalin in an open-label study at doses 225-900 mg. RESULTS: All patients discontinued successfully BDZ in 3-14 weeks, moreover with a significant reduction of their previous anxiety levels under BDZ. In addition, patients showed also a significant amelioration in their cognitive functioning. Pregabalin's side-effects were mild and transient, lasting only during the first 2 weeks of treatment. CONCLUSION: Although preliminary, our findings suggest that pregabalin may be one new promising agent in the treatment of BDZ dependence.

Ontological assumptions of psychiatric taxonomy: main rival positions and their critical assessment.

The scientific classification of human psychopathology raises a host of important philosophical issues ranging over all major areas of philosophical inquiry; logic, semantics, ontology, epistemology and ethics. The paper focuses on the major views of the ontological status of our psychodiagnostic constructs; idealism, nominalism and finally, neoaristotelian realism. Idealism holds that our psychodiagnostic constructs represent ideal essences, instantiated imperfectly by individual mental patients of the same psychodiagnostic class. These ideal essences are construed either as abstract forms dwelling in an autonomous realm of eternal abstract objects--platonistic idealism--or as ideal objects emerging in and grasped directly by a pure or absolute consciousness--husserlian idealism. By contrast, nominalism claims that our psychodiagnostic constructs are nothing but conventional common names of sets of individual mental patients, invented and adopted on purely pragmatic grounds such as their practical utility, especially in predicting their clinical course and outcome under various types of treatment. Finally, neoaristotelian realism holds that, though our psychodiagnostic constructs are concepts, and thus of our own making, they are not arbitrary ones but grounded in objective features shared by individual mental patients of a given psychodiagnostic class. It is argued that both idealism and nominalism are flawed and thus untenable--though for different reasons--and a refined version of neoaristotelian realism defended.

The safety of the electroconvulsive therapy-escitalopram combination.

It has been suggested that the efficacy of electroconvulsive therapy (ECT) in the treatment of major depressive episodes may be enhanced by concurrent administration of antidepressant medication. Therefore, the issue of how safe the combination of these 2 treatment modalities is warrants investigation. Escitalopram (ESC) is a novel selective serotonin reuptake inhibitor that seems to have a favorable side effect profile. To the best of our knowledge, there is no report on the safety of the ECT-ESC combination. We report the cases of 3 female inpatients with major depressive episode--two in the context of major depressive disorder and one in the context of bipolar disorder I--who underwent ECT while concurrently receiving ESC (20 mg/d) as part of their regimen. In all cases, the combination was well tolerated, and only minimal side effects were reported.

The safety of the electroconvulsive therapy-aripiprazole combination: four case reports.

In clinical practice, a proportion of patients with psychotic or mood disorders are treated with electroconvulsive therapy (ECT) while receiving concomitantly antipsychotic and/or other psychotropic agents. Aripiprazole is a second-generation antipsychotic that seems to have a favorable side-effect profile. However, to the best of our knowledge, there are, as yet, no available reports on the safety of ECT-aripiprazole combination. We report the cases of 4 female inpatients--3 suffering from major depression and 1 from schizophrenia--who underwent ECT--1 of them twice--while receiving aripiprazole (10-15 mg/d), as part of their regimen. In all cases, the combination was well tolerated and only minimal side effects were reported.