Pregabalin for the treatment of generalized anxiety disorder: an update

A previous review summarized what was then known about the potential role of pregabalin in the treatment of patients with generalized anxiety disorder (GAD): this review provides an update on its pharmacological properties and presumed mechanism of action, the liability for abuse, and efficacy and tolerability in patients with GAD. Pregabalin has a similar molecular structure to the inhibitory neurotransmitter gamma amino butyric acid (GABA) but its mechanism of action does not appear to be mediated through effects on GABA. Instead, its anxiolytic effects may arise through high-affinity binding to the alpha-2-delta sub-unit of the P/Q type voltage-gated calcium channel in “over-excited” presynaptic neurons, thereby reducing the release of excitatory neurotransmitters such as glutamate. The findings of randomized controlled trials and meta-analyses together indicate that pregabalin is efficacious in both acute treatment and relapse prevention in GAD, with some evidence of an early onset of effect, and broad efficacy in reducing the severity of psychological and physical symptoms of anxiety. It also has efficacy as an augmenting agent after non-response to antidepressant treatment in GAD. Continuing vigilance is needed in assessing its potential abuse liability but the tolerability profile of pregabalin may confer some advantages over other pharmacological treatments in the short term for treatment in patients with GAD

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 () or NA-MDD () 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

Oxcarbazepine as monotherapy of acute mania in insufficiently controlled type-1 diabetes mellitus: a case-report

<p>Abstract</p> <p>Background</p> <p>Type-1 diabetes mellitus (DM) is a lifelong serious condition which often renders the application of standard treatment options for patients' comorbid conditions, such as bipolar disorder I, risky – especially for acute manic episodes. We present such a case whereby the application of standard anti-manic treatments would have jeopardized a patient whose physical condition was already compromised by DM.</p> <p>Methods</p> <p>We report the case of a 55-year-old female with a history of type-1 DM since the age of 11, and severe ocular and renal vascular complications thereof. While on the waiting list for pancreatic islet cell transplantation, she developed a manic episode that proved recalcitrant to a treatment with gabapentin, lorazepam and quetiapine. Moreover, her mental state affected adversely her already compromised glycemic control, requiring her psychiatric hospitalization. Her psychotropic medication was almost discontinued and replaced by oxcarbazepine (OXC) up to 1800 mg/day for 10 days.</p> <p>Results</p> <p>The patient's mental state improved steadily and on discharge, 3 weeks later, she showed an impressive improvement rate of over 70% on the YMRS. Moreover, she remains normothymic 6 months after discharge, with OXC at 1200 mg/day.</p> <p>Conclusion</p> <p>Standard prescribing guidelines for acute mania recommend a combination of an antipsychotic with lithium or, alternatively, a combination of an antipsychotic with valproate or carbamazepine. However, in our case, administration of lithium was at least relatively contra-indicated because of patient's already compromised renal function. Furthermore, antipsychotics increase glucose levels and thus were also relatively contra-indicated. Moreover, the imminent post-transpantation immunosupressant treatment with immuno-modulating medicines also contra-indicated both valproate and carbamazepine. Despite the severe methodological limitations of case reports in general, the present one suggests that OXC as monotherapy might be both safe and efficacious in the treatment of acute mania in patients with early-onset type-1 DM, whose already compromised physical condition constitutes an absolute or relative contra-indication for the administration of standard treatments, though there are no, as yet, randomized clinical trials attesting to its efficacy unambiguously.</p

Prevention of suicide by Clozapine in mental disorders:: a systematic review

Background: previous research has investigated the efficacy of clozapine in reducing suicidality in patients with schizophrenia and schizoaffective disorder. We aimed to systematically review published evidence, including studies concerning clozapine administration to treat: (a) refractory suicidality in other mental disorders, including bipolar disorder and borderline and other personality disorders; and (b) refractory cases of non-suicidal self-injury. Method: we performed a PUBMED-search (last day: July 17, 2022) of English-language studies, combining the keywords “clozapine”, “suicidality” and “suicide” with various psychopathological terms (e.g. “schizophrenia”). All duplications were eliminated. Results: fifty-one studies were eligible for inclusion in the review. Most studies suggest a superior anti-suicide effect of clozapine in schizophrenia/schizoaffective disorder, compared to other antipsychotics, or no antipsychotic therapy, which is not due to the close monitoring of patients for blood dyscrasias. No consensus exists as to whether other antipsychotic drugs share this effect. Discontinuation of clozapine is associated with increases in suicidality. Reductions in refractory suicidality/NSSI are observed in clozapine-treated patients with bipolar disorder or borderline personality disorder, but the evidence is limited. Potential biological underpinnings of the anti-suicide effect of clozapine include its unique profile of modulation of brain neurotransmitters; its non-selectivity for neurotransmitter receptors; specific genetic and hormonal factors; effects on neuroinflammation; and ability to elicit epileptiform activity. Conclusion: the superior antisuicidal effect of clozapine in schizophrenia/schizoaffective disorder patients is well established. It may have a role in severe and refractory cases of suicidality and non-suicidal self-injury in patients with bipolar disorder or borderline personality disorder, but the level and quality of supporting evidence is limited

Anticonvulsant and antipsychotic medications in the pharmacotherapy of panic disorder:: a structured review

Background: as the remission rate of panic disorder (PD) achieved with conventional pharmacotherapy ranges between 20-50%, alternative psychopharmacological strategies are needed. We aimed to firstly review data regarding use of antipsychotic and non-benzodiazepine anticonvulsant medication in PD patients with or without comorbidities; secondly, to review data concerning reduction of panic symptoms during treatment of another psychiatric disorder with the same medications; and thirdly, to examine reports of anticonvulsant- or antipsychotic-induced new-onset panic symptomatology. Method: we performed a PUBMED-search (last day: April 28, 2020) of only English-language studies, combining psychopathological terms (e.g. “panic disorder”) and terms referring either to categories of psychotropic medications (e.g. “anticonvulsants”) or to specific drugs (e.g. “carbamazepine”). All duplications were eliminated. All studies included in the review met certain inclusion/exclusion criteria. The level of evidence for the efficacy of each drug was defined according to widely accepted criteria.Results: in treatment-resistant PD, beneficial effects have been reported after treatment (mostly augmentation therapy) with a range of anticonvulsant (carbamazepine, gabapentin, lamotrigine, levetiracetam, oxcarbamazepine, valproate, vigabatrin, tiagabine) and antipsychotic (aripiprazole, olanzapine, risperidone, sulpiride) medications: overall, most medications appear generally well tolerated. Additionally, bipolar patients receiving valproate or quetiapine-XR (but not risperidone or ziprasidone) demonstrated reductions of comorbid panic-related symptoms. There are case reports of new-onset panic symptoms associated with clozapine, haloperidol, olanzapine and topiramate, in patients with conditions other than PD. The small-to-modest sample size, the lack of control groups and the open-label and short-term nature of most of the reviewed studies hinder definitive conclusions regarding either the short-term and long-term efficacy of antipsychotic and anticonvulsant medications or their potential long-term side effects.Conclusion: some atypical antipsychotic and anticonvulsant medications may have a role in the treatment of some PD patients, mostly when more conventional approaches have not been successful, but the quality of supporting evidence is limited. <br/

Anticonvulsant and antipsychotic medications in the pharmacotherapy of panic disorder: a structured review

Background: As the remission rate of panic disorder (PD) achieved with conventional pharmacotherapy ranges between 20% and 50%, alternative psychopharmacological strategies are needed. We aimed to firstly review data regarding use of antipsychotic and non-benzodiazepine anticonvulsant medication in PD patients with or without comorbidities; secondly, to review data concerning reduction of panic symptoms during treatment of another psychiatric disorder with the same medications; and thirdly, to examine reports of anticonvulsant- or antipsychotic-induced new-onset panic symptomatology. Methods: We performed a PubMed search (last day: 28 April 2020) of English-language studies only, combining psychopathological terms (e.g. ‘panic disorder’) and terms referring either to categories of psychotropic medications (e.g. ‘anticonvulsants’) or to specific drugs (e.g. ‘carbamazepine’). All duplications were eliminated. All studies included in the review met certain inclusion/exclusion criteria. The level of evidence for the efficacy of each drug was defined according to widely accepted criteria. Results: In treatment-resistant PD, beneficial effects have been reported after treatment (mostly augmentation therapy) with a range of anticonvulsant (carbamazepine, gabapentin, lamotrigine, levetiracetam, oxcarbamazepine, valproate, vigabatrin, tiagabine) and antipsychotic (aripiprazole, olanzapine, risperidone, sulpiride) medications: overall, most medications appear generally well tolerated. Additionally, bipolar patients receiving valproate or quetiapine-XR (but not risperidone or ziprasidone) demonstrated reductions of comorbid panic-related symptoms. There are case reports of new-onset panic symptoms associated with clozapine, haloperidol, olanzapine and topiramate, in patients with conditions other than PD. The small-to-modest sample size, the lack of control groups and the open-label and short-term nature of most of the reviewed studies hinder definitive conclusions regarding either the short-term and long-term efficacy of antipsychotic and anticonvulsant medications or their potential long-term side effects. Conclusion: Some atypical antipsychotic and anticonvulsant medications may have a role in the treatment of some PD patients, mostly when more conventional approaches have not been successful, but the quality of supporting evidence is limited

Lack of specific association between panicogenic properties of caffeine and HPA-axis activation. A placebo-controlled study of caffeine challenge in patients with panic disorder

A subgroup of patients with Panic Disorder (PD) exhibits increased sensitivity to caffeine administration. However, the association between caffeine-induced panic attacks and post-caffeine hypothalamic pituitary adrenal (HPA)-axis activation in PD patients remains unclear. In a randomized, double-blind, cross-over experiment, 19 PD patients underwent a 400-mg caffeine-challenge and a placebo-challenge, both administered in the form of instant coffee. Plasma levels of adrenocorticotropic hormone (ACTH), cortisol and dehydroepiandrosterone sulfate (DHEAS) were assessed at both baseline and post-challenge. No patient panicked after placebo-challenge, while nine patients (47.3%) panicked after caffeine-challenge. Placebo administration did not result in any significant change in hormones’ plasma levels. Overall, sample’s patients demonstrated significant increases in ACTH, cortisol, and DHEAS plasma levels after caffeine administration. However, post-caffeine panickers and non-panickers did not differ with respect to the magnitude of the increases. Our results indicate that in PD patients, caffeine-induced panic attacks are not specifically associated with HPA-axis activation, as this is reflected in post-caffeine increases in ACTH, cortisol and DHEAS plasma levels, suggesting that caffeine-induced panic attacks in PD patients are not specifically mediated by the biological processes underlying fear or stress. More generally, our results add to the evidence that HPA-axis activation is not a specific characteristic of panic. (C) 2015 Elsevier Ireland Ltd. All rights reserved

Pregabalin in Zolpidem Dependence and Withdrawal

Several recent reports attest to zolpidem’s strong potential for abuse, dependence, and severe withdrawal symptoms upon its discontinuation. We report, for the first time, on 1 case of heavy zolpidem abuse and dependence with severe withdrawal symptoms twice treated safely and successfully with pregabalin, a newer antiepileptic agent devoid of known strong potential for abuse and dependence

Lamotrigine Administration in Panic Disorder With Agoraphobia

Several anticonvulsants, although as yet not lamotrigine (LTG), have been found useful in the treatment of panic disorder with (PDA) or without agoraphobia. We administered LTG (200 mg/d) to 4 outpatients with PDA, as an augmentation therapy (3 patients with chronic and severe agoraphobia) or monotherapy (1 drug-naive patient with first-onset PDA) in a 14-week trial. The patient under LTG monotherapy improved significantly, whereas PDA symptoms in 2 of the other patients improved to some extent

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