Pharmacological approaches to the management of panic disorder in older patients: a systematic review.

INTRODUCTION: Recommendations for treating panic disorder (PD) in older patients are scarce. The authors have systematically reviewed whether several recommended medications are superior to others and their optimal doses in this age group. METHODS: A database search of studies involving patients with PD with/without agoraphobia aged ≥ 60 years was carried out using PubMed, PsycINFO, Embase, and Clinical Trials.gov, from their inception dates to 1 March 2023. Only four (published from 2002 to 2010) of the 1292 records screened were included. A risk of bias assessment was provided. This systematic review was performed using The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). RESULTS: Two studies were randomized clinical trials, whereas two were open-label, including paroxetine, citalopram, escitalopram, and sertraline; three studies reported short-term evaluations, whereas one study included a 26-week follow-up. Medications provided benefits, with good tolerability. Preliminary results suggested greater benefits of paroxetine in reducing panic attacks vs. cognitive - behavioral therapy, and an earlier decrease in PAs with escitalopram vs. citalopram. Risk of bias was considerable. CONCLUSIONS: The pharmacological management of PD in older patients has received no attention. Findings are scant, dated, and affected by methodological flaws; thus, they do not provide significant advances.

Cardiorespiratory Assessments in Panic Disorder Facilitated by Wearable Devices: A Systematic Review and Brief Comparison of the Wearable Zephyr BioPatch with the Quark-b2 Stationary Testing System.

Abnormalities in cardiorespiratory measurements have repeatedly been found in patients with panic disorder (PD) during laboratory-based assessments. However, recordings performed outside laboratory settings are required to test the ecological validity of these findings. Wearable devices, such as sensor-imbedded garments, biopatches, and smartwatches, are promising tools for this purpose. We systematically reviewed the evidence for wearables-based cardiorespiratory assessments in PD by searching for publications on the PubMed, PsycINFO, and Embase databases, from inception to 30 July 2022. After the screening of two-hundred and twenty records, eight studies were included. The limited number of available studies and critical aspects related to the uncertain reliability of wearables-based assessments, especially concerning respiration, prevented us from drawing conclusions about the cardiorespiratory function of patients with PD in daily life. We also present preliminary data on a pilot study conducted on volunteers at the Villa San Benedetto Menni Hospital for evaluating the accuracy of heart rate (HR) and breathing rate (BR) measurements by the wearable Zephyr BioPatch compared with the Quark-b2 stationary testing system. Our exploratory results suggested possible BR and HR misestimation by the wearable Zephyr BioPatch compared with the Quark-b2 system. Challenges of wearables-based cardiorespiratory assessment and possible solutions to improve their reliability and optimize their significant potential for the study of PD pathophysiology are presented.

Therapeutic Drug Monitoring of Antidepressants: An Underused but Potentially Valuable Tool in Primary Care.

Depressive disorders are among the most burdensome diseases globally in terms of prevalence, as well as in terms of quality of life, morbidity, and mortality. Hence, it is becoming increasingly common for primary care physicians to administer and monitor the treatment of individuals affected by depressive disorders. In this framework, Therapeutic Drug Monitoring (TDM) comes to the forefront. TDM is the measurement of specific drugs in the blood or plasma/serum, and its usefulness lies in the fact that it allows physicians to assess drug levels to personalize and optimize treatments. TDM has been used for decades to measure several classes of psychotropic drugs, such as antiepileptics and antipsychotics, but the use of this tool is still in its infancy in regard to antidepressants. In the context of primary care, TDM of antidepressant drug treatment shows promise, as it can enable primary care physicians to monitor the safety and efficacy of the treatment, leaving to secondary care, i.e., psychiatrists, the management of the more complex clinical cases.

Social withdrawal and neurocognitive correlates in schizophrenia.

Poor neurocognitive performance has been associated with poor functional outcome in schizophrenia (SCZ) in past studies. Nonetheless, the likely association between neurocognition and social withdrawal has never been investigated. The aim of our study was to investigate in a large and heterogeneous sample of SCZ patient cross-sectional associations between neurocognitive domains and social withdrawal. The sample included 761 SCZ patients who completed the baseline visit in the CATIE study. Neurocognition was assessed by a comprehensive battery of tests resulting in five domain scores and a composite score. Social withdrawal was measured by a specific item of the Heinrichs-Carpenter Quality of Life Scale. Social withdrawal was associated with a lower score in the neurocognitive composite score and in 'Verbal memory,' 'Processing speed' and 'Working memory' scores. 'Verbal memory' score showed the strongest association with social withdrawal. Eight percent of the total variance of social withdrawal was explained by these three cognitive domains and additional clinical and sociodemographic factors (education years, PANSS positive symptoms score, and employment). Our results confirmed the wide heterogeneity and specificity of the correlation between neurocognitive domains and indicators of functional outcome in SCZ, underlining the role of certain neurocognitive abilities in social withdrawal.

Venlafaxine and O-desmethylvenlafaxine serum levels are positively associated with antidepressant response in elder depressed out-patients.

BACKGROUND: Therapeutic Drug Monitoring (TDM) represents one of the most promising tools in clinical practice to optimise antidepressant treatment. Nevertheless, little is still known regarding the relationship between clinical efficacy and serum concentration of venlafaxine (VEN). The aim of our study was to investigate the association between serum concentration of venlafaxine + O-desmethylvenlafaxine (SCVO) and antidepressant response (AR). METHODS: 52 depressed outpatients treated with VEN were recruited and followed in a naturalistic setting for three months. Hamilton Depression Rating Scale-21 was administered at baseline, at month 1 and at month 3 to assess AR. SCVO was measured at steady state. Linear regression analysis and nonlinear least-squares regression were used to estimate association between SCVO and AR. RESULTS: Our results showed an association between AR and SCVO that follows a bell-shaped quadratic function with a progressive increase of AR within the therapeutic reference range of SCVO (i.e. 100-400 ng/mL) and a subsequent decrease of AR at higher serum levels. DISCUSSION: This study strongly suggests that TDM could represent a more appropriate tool than the oral dosage to optimise the treatment with VEN. Specifically, highest efficacy might be achieved by titrating patients at SCVO levels around 400 ng/mL.

Antidepressant efficacy is correlated with plasma levels: mega-analysis and further evidence.

The debate around optimal target dose for first-line antidepressants (ADs) is still ongoing. Along this line, therapeutic drug monitoring (TDM) represents one of the most promising tools to improve clinical outcome. Nevertheless, a few data exist regarding the concentration-effect relationship of first-line ADs which limits TDM implementation in routine clinical practice. We conducted the first patient-level concentration-response mega-analysis including data acquired by us previously and explored the concentration dependency of first-line AD (206 subjects). Further, new data on mirtazapine are reported (18 subjects). Hamilton Depression Rating Scale-21 administered at baseline, at month 1 and month 3 was used as the measure of efficacy to assess antidepressant response (AR). When pooling all four first-line ADs together, normalized plasma levels and AR significantly fit a bell-shaped quadratic function with a progressive increase of AR up to around the upper normalized limit of the therapeutic reference range with a decrease of AR at higher serum levels. Our results complement the available evidence on the issue and the recent insights gained from dose-response studies. A concentration-dependent clinical efficacy, such as previously demonstrated for tricyclic compounds, also emerge for first-line ADs. Our study supports a role for TDM as a tool to optimize AD treatment to obtain maximum benefit.

Eating disorders: Do PET and SPECT have a role? A systematic review of the literature.

A systematic review was implemented according to PRISMA guidelines on Pubmed, Psychinfo, Medline, Embase to fill the existing literature gap on the effectiveness of using Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) in Anorexia Nervosa (AN), Bulimia Nervosa (BN) and Binge Eating Disorder (BED). Twenty-two articles were included. Four studies reported an increased density in 5-hydroxytryptamine receptor (5-HT1A) in fronto-temporo-parietal regions in both affected and recovered AN as well as in BN. The 5-HT transporter (5-HTT) binding was increased or diminished in different specific cortical areas and in relation to Eating Disorder (ED) subtypes. Some evidences of blunted Dopamine (DA) release in the putamen in BN patients suggest that their DA function might be impaired as in addictive behaviours. Studies estimating the regional Cerebral Blood Flow (rCBF) with SPECT demonstrated that temporal areas seem to play a key role in ED corroborating the hypothesis of a cingulate-temporal cortical dysfunction in AN. In addition, alterations of both parietal and prefrontal cortex provide a possible common neural substrate in AN. Studies included in this review are heterogeneous preventing robust conclusions, however, our findings add knowledge on some of the neurotransmitters involved in ED.

Duloxetine plasma level and antidepressant response.

BACKGROUND: Major Depressive Disorder (MDD) is associated with a high rate of inadequate treatment response, which is mainly due to the large inter-individual genetic variability in pharmacokinetic and pharmacodynamic targets of antidepressant drugs. Little is still known about the exact association between plasma level of first-line antidepressants and clinical response. This is particularly true for duloxetine, a dual serotonin and norepinephrine reuptake inhibitor recommended as first-line treatment for MDD. The aim of this study was to investigate the association between serum concentration of duloxetine (SCD) and antidepressant response (AR). METHODS: 66 MDD patients treated with duloxetine 60 mg/day monotherapy were recruited in an outpatient setting and followed for three months. Hamilton Depression Rating Scale - 21 (HAMD-21) was administrated at baseline, at month 1, and at month 3 to assess AR. SCD was measured at steady state. Linear regression analysis and nonlinear least-squares regression were used to estimate association between SCD and AR. RESULTS: SCD showed a high inter-individual variability in our sample, despite the duloxetine fixed oral dosage. We found a strong association between SCD and AR following a bell-shaped function at month 1 and at month 3. Nonetheless, within the recommended SCD range of 30-120 ng/mL a more linear correlation between SCD and AR was observed. DISCUSSION: Our results suggest that for duloxetine the association between SCD and AR likely follows a bell-shaped quadratic function with poor AR at subtherapeutic SCD and progressive decrease of AR at higher SCD. The maximum antidepressant efficacy seems to require SCD values next to the highest recommended SCD (30-120 ng/mL), probably because of the optimal saturation of both serotonin and norepinephrine transporters. Thus, taking into account the observed high interindividual variability of SCD, our findings suggest that for MDD patients treated with duloxetine, SCD could be a useful tool to guide the treatment by optimizing the oral dosage in order to increase the AR rate.