Effect of Quetiapine and Norquetiapine on Anxiety and Depression in Major Psychoses Using a Pharmacokinetic Approach

Altamura, Alfredo Carlo; Moliterno, D.; Paletta, Silvia; Buoli, Massimiliano; Dell’Osso, Bernardo; Mauri, Massimo C.; Bareggi, Silvio R.

doi:10.2165/11597330-000000000-00000

Cited by 28 publications

(22 citation statements)

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“…In particular, N-QTP, a potent norepinephrine reuptake inhibitor and partial serotonin 5-HT 1A receptor agonist, has been suggested as a putative mediator of QTP antidepressant activity (Altamura et al, 2012[1]).…”

Section: Introductionmentioning

confidence: 99%

Clinical Pharmacokinetics of Atypical Antipsychotics: An Update

et al. 2018

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Therapeutic drug monitoring studies have generally concentrated on controlling compliance and avoiding side effects by maintaining long-term exposure to minimally effective blood concentrations. The rationale for using therapeutic drug monitoring in relation to second-generation antipsychotics is still being discussed at least with regard to the real clinical utility, but there is evidence that it can improve efficacy, especially when patients do not respond or develop side effects using therapeutic doses. Furthermore, drug plasma concentration determinations can be of some utility in medico-legal problems. This review concentrates on the clinical pharmacokinetic data related to clozapine, risperidone, paliperidone, olanzapine, quetiapine, amisulpride, ziprasidone, aripiprazole, sertindole, asenapine, iloperidone, lurasidone, brexpiprazole and cariprazine and briefly considers the main aspects of their pharmacodynamics. Optimal plasma concentration ranges are proposed for clozapine, risperidone, paliperidone and olanzapine because the studies of quetiapine, amisulpride, asenapine, iloperidone and lurasidone provide only limited information and there is no direct evidence concerning ziprasidone, aripiprazole, sertindole, brexpiprazole and cariprazine: the few reported investigations need to be confirmed and extended.

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Section: Introductionmentioning

confidence: 99%

Clinical Pharmacokinetics of Atypical Antipsychotics: An Update

et al. 2018

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“…When the patient has taken the extended release (ER) formulation in the evening and blood was withdrawn in the morning, expected concentrations are 2-fold higher than trough levels [25,183,356,400,482,492,851,907,1100,1252,1312]. …”

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Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017

Bergemann²,

et al. 2017

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Therapeutic drug monitoring (TDM) is the quantification and interpretation of drug concentrations in blood to optimize pharmacotherapy. It considers the interindividual variability of pharmacokinetics and thus enables personalized pharmacotherapy. In psychiatry and neurology, patient populations that may particularly benefit from TDM are children and adolescents, pregnant women, elderly patients, individuals with intellectual disabilities, patients with substance abuse disorders, forensic psychiatric patients or patients with known or suspected pharmacokinetic abnormalities. Non-response at therapeutic doses, uncertain drug adherence, suboptimal tolerability, or pharmacokinetic drug-drug interactions are typical indications for TDM. However, the potential benefits of TDM to optimize pharmacotherapy can only be obtained if the method is adequately integrated in the clinical treatment process. To supply treating physicians and laboratories with valid information on TDM, the TDM task force of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) issued their first guidelines for TDM in psychiatry in 2004. After an update in 2011, it was time for the next update. Following the new guidelines holds the potential to improve neuropsychopharmacotherapy, accelerate the recovery of many patients, and reduce health care costs.

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“…Recently, norquetiapine has been found to be a potent inhibitor for norepinephrine transporter shared commonality with TCAs and SNRIs, and a moderate-to-high affinity for D2, 5HT1A, 5HT2A, and 5HT2C receptors shared some properties with SSRIs [20,21]. These mechanisms of action may explain its efficacy for the treatment of depression and anxiety [21-24]. …”

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confidence: 99%

Quetiapine monotherapy in acute phase for major depressive disorder: a meta-analysis of randomized, placebo-controlled trials

Maneeton

Srisurapanont

et al. 2012

BMC Psychiatry

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BackgroundSchizophrenia and bipolar depression trials suggest that quetiapine may have an antidepressant effect.ObjectivesThis meta-analysis aimed to determine the efficacy, acceptability and tolerability of quetiapine treatment for major depressive disorder (MDD). Only the randomized controlled trials (RCTs) comparison between quetiapine and placebo were included. The authors searched such clinical trials carried out between 1991 and February 2012.Data sourcesMEDLINE, EMBASE, CINHL, PsycINFO and Cochrane Controlled Trials Register were searched in February 2012. Study populations comprised adults with MDD or major depression.Study eligible criteria, participants and interventionsEligible studies were randomized, placebo-controlled trials of quetiapine monotherapy carried out in adults with MDD and presenting endpoint outcomes relevant to: i) depression severity, ii) response rate, iii) overall discontinuation rate, or iv) discontinuation rate due to adverse events. No language restriction was applied.Study appraisal and synthesis methodsAll abstracts identified by the electronic searches were examined. The full reports of relevant studies were assessed, and the data of interest were extracted. Based on the Cochrane methods of bias assessment, risks of bias were determined. The studies with two risks or less were included. The efficacy outcomes were the mean change scores of depression rating scales, the overall response rate, and the overall remission rates. The overall discontinuation rate was considered as a measure of acceptability. The discontinuation rate due to adverse events was a measure of tolerability. Relative risks (RRs) and weighted mean differences (WMDs) with 95% confidence intervals (CIs) were computed by using a random effect model.ResultsA total of 1,497 participants in three RCTs were included. All trials examined the quetiapine extended-release (XR). The pooled mean change scores of the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating Scale (HAM-D) of the quetiapine-treated group were higher than those of the placebo-treated group with the WMDs (95%CI) of -3.37 (-3.95, -2.79) and -2.46 (-3.47, -1.45), respectively. All studies defined the response and remission as ≥ 50% reduction of the MADRS total score and the MADRS total score of ≤8 at endpoint, respectively. The overall response and remission rates were significantly greater in the quetiapine-treated group with RRs (95%CIs) of 1.44 (1.26, 1.64) and 1.37 (1.12, 1.68), respectively. The pooled discontinuation rate was not significantly different between groups with an RR (95%CI) of 1.16 (0.97, 1.39). The pooled discontinuation rate due to adverse event was greater in the quetiapine group with an RR (95%CI) of 2.90 (1.87, 4.48). With respect to sleep time, the pooled mean change Pittsburgh Sleep Quality Index (PSQI) scores of the quetiapine-treated group was also significantly higher than that of the placebo-treated group [WMD (95%CI) of -1.21 (-1.81, -0.61)].LimitationsVariety of quetiapine XR doses and t...

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Effect of Quetiapine and Norquetiapine on Anxiety and Depression in Major Psychoses Using a Pharmacokinetic Approach

Abstract: The results of this study confirm the efficacy of quetiapine on both anxious and depressive symptoms. Norquetiapine has a specific effect on anxiety and depressive symptoms, showing a correlation between plasma concentrations and clinical efficacy only in patients with bipolar depression.

Cited by 28 publications

References 28 publications

Clinical Pharmacokinetics of Atypical Antipsychotics: An Update

Clinical Pharmacokinetics of Atypical Antipsychotics: An Update

Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017

Quetiapine monotherapy in acute phase for major depressive disorder: a meta-analysis of randomized, placebo-controlled trials

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