Pharmaceuticals

Research

19 pages, 738 KiB

Open AccessArticle

An Experimental Medicine Investigation of the Effects of Subacute Pramipexole Treatment on Emotional Information Processing in Healthy Volunteers

by Marieke Annie Gerdine Martens, Alexander Kaltenboeck, Don Chamith Halahakoon, Michael Browning, Philip J. Cowen and Catherine J. Harmer

Pharmaceuticals 2021, 14(8), 800; https://doi.org/10.3390/ph14080800 - 14 Aug 2021

Cited by 9 | Viewed by 3258

Abstract

Treatment with the dopamine D2/D3 receptor agonist pramipexole has demonstrated promising clinical effects in patients with depression. However, the mechanisms through which pramipexole might alleviate depressive symptoms are currently not well understood. Conventional antidepressant drugs are thought to work by biasing the processing [...] Read more.

Treatment with the dopamine D2/D3 receptor agonist pramipexole has demonstrated promising clinical effects in patients with depression. However, the mechanisms through which pramipexole might alleviate depressive symptoms are currently not well understood. Conventional antidepressant drugs are thought to work by biasing the processing of emotional information in favour of positive relative to negative appraisal. In this study, we used an established experimental medicine assay to explore whether pramipexole treatment might have a similar effect. Employing a double-blind, parallel-group design, 40 healthy volunteers (aged 18 to 43 years, 50% female) were randomly allocated to 12 to 15 days of treatment with either pramipexole (at a peak daily dose of 1.0 mg pramipexole salt) or placebo. After treatment was established, emotional information processing was assessed on the neural level by measuring amygdala activity in response to positive and negative facial emotional expressions, using functional magnetic resonance imaging (MRI). In addition, behavioural measures of emotional information processing were collected at baseline and on drug, using an established computerized task battery, tapping into different cognitive domains. As predicted, pramipexole-treated participants, compared to those receiving placebo, showed decreased neural activity in response to negative (fearful) vs. positive (happy) facial expressions in bilateral amygdala. Contrary to our predictions, however, pramipexole treatment had no significant antidepressant-like effect on behavioural measures of emotional processing. This study provides the first experimental evidence that subacute pramipexole treatment in healthy volunteers modifies neural responses to emotional information in a manner that resembles the effects of conventional antidepressant drugs. Full article

(This article belongs to the Special Issue Psychopharmacology of Affective Disorders)

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11 pages, 705 KiB

Open AccessArticle

Electroconvulsive Therapy and Age: Effectiveness, Safety and Tolerability in the Treatment of Major Depression among Patients under and over 65 Years of Age

by Monika Dominiak, Anna Z. Antosik-Wójcińska, Marcin Wojnar and Paweł Mierzejewski

Pharmaceuticals 2021, 14(6), 582; https://doi.org/10.3390/ph14060582 - 18 Jun 2021

Cited by 12 | Viewed by 4374

Abstract

Electroconvulsive therapy (ECT) remains the most effective therapy in treatment-resistant depression. However, the safety of ECT has been consistently questioned, particularly among elderly patients. We assessed the efficacy and safety of ECT in patients before and after 65 years old. The study was [...] Read more.

Electroconvulsive therapy (ECT) remains the most effective therapy in treatment-resistant depression. However, the safety of ECT has been consistently questioned, particularly among elderly patients. We assessed the efficacy and safety of ECT in patients before and after 65 years old. The study was conducted between 2015 and 2018 and included 91 patients (61 under and 29 over 65 years old) with major depression undergoing ECT. The Hamilton Depression Rating Scale was used to evaluate efficacy. Cognitive functions were assessed using: MMSE, RAVLT, Trail Making Test, Stroop Test and Autobiographical Memory Interview-Short Form. ECT was more effective in older patients as compared to younger (p < 0.001). No serious adverse events were observed in either group. Increased blood pressure and arrhythmias were more common in the older compared to the younger group (p = 0.044 and p = 0.047, respectively), while disturbances of consciousness did not differ between groups (p = 0.820). Most of the cognitive functions remained unchanged compared to baseline, whereas the outcomes of MMSE, RAVLT and Stroop tests showed greater improvements in the older compared to the younger group (all p < 0.05). The decline in the retrieval consistency of autobiographical memory was more pronounced in the younger group (p = 0.024). ECT is a highly effective, safe and well-tolerated method of treating depression regardless of age. Full article

(This article belongs to the Special Issue Psychopharmacology of Affective Disorders)

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15 pages, 3187 KiB

Open AccessArticle

Functional Connectivity between Task-Positive Networks and the Left Precuneus as a Biomarker of Response to Lamotrigine in Bipolar Depression: A Pilot Study

by Marieke Martens, Nicola Filippini, Charles Masaki and Beata R. Godlewska

Pharmaceuticals 2021, 14(6), 534; https://doi.org/10.3390/ph14060534 - 3 Jun 2021

Cited by 11 | Viewed by 3684

Abstract

Treatment of bipolar depression poses a significant clinical challenge. Lamotrigine is one of a few efficacious drugs, however, it needs to be titrated very slowly and response can only be assessed after 10–12 weeks. With only a proportion of patients responding, an exploration [...] Read more.

Treatment of bipolar depression poses a significant clinical challenge. Lamotrigine is one of a few efficacious drugs, however, it needs to be titrated very slowly and response can only be assessed after 10–12 weeks. With only a proportion of patients responding, an exploration of factors underlying treatment responsivity is of paramount clinical importance, as it may lead to an allocation of the drug to those most likely to respond to it. This study aimed at identifying differences in patterns of pre-treatment resting state functional connectivity (rsFC) that may underlie response to lamotrigine in bipolar depression. After a baseline MRI scan, twenty-one patients with bipolar depression were treated with lamotrigine in an open-label design; response, defined as ≥50% decrease in Hamilton Depression Rating Scale (HAMD) score, was assessed after 10–12 weeks of treatment. Twenty healthy controls had a baseline clinical assessment and scan but did not receive any treatment. Fifteen out of 21 (71%) patients responded to lamotrigine. Treatment responsivity was associated with enhanced pre-treatment rsFC of the right fronto-parietal network (FPN) and dorsal attention network (DAN) with left precuneus. The lack of treatment response was additionally characterised by reduced rsFC: of the DAN with right middle temporal gyrus; of the default mode network (DMN) with left precuneus; of the extended sensory-motor area with areas including the left hippocampus/left amygdala and left subcallosal cortex/nucleus accumbens; and of the left FPN with left inferior temporal gyrus/occipital fusiform gyrus/lateral occipital cortex. The results suggest that preserved rsFC between the FPN and DAN, the networks involved in cognitive control, and the hub of the posterior DMN, the left precuneus, may be critical for good response to lamotrigine as an add-on treatment in patients with bipolar depression. The study also suggests a more general decrease in rsFC to be related to poor treatment responsivity. Full article

(This article belongs to the Special Issue Psychopharmacology of Affective Disorders)

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9 pages, 1019 KiB

Open AccessCommunication

Symptom Cluster-Matching Antidepressant Treatment: A Case Series Pilot Study

by Sławomir Murawiec and Marek Krzystanek

Pharmaceuticals 2021, 14(6), 526; https://doi.org/10.3390/ph14060526 - 31 May 2021

Cited by 3 | Viewed by 3143

Abstract

Despite treating depression with antidepressants, their effectiveness is often insufficient. Comparative effectiveness studies and meta-analyses show the effectiveness of antidepressants; however, they do not provide clear indications as to the choice of a specific antidepressant. The rational choice of antidepressants may be based [...] Read more.

Despite treating depression with antidepressants, their effectiveness is often insufficient. Comparative effectiveness studies and meta-analyses show the effectiveness of antidepressants; however, they do not provide clear indications as to the choice of a specific antidepressant. The rational choice of antidepressants may be based on matching their mechanisms of action to the symptomatic profiles of depression, reflecting the heterogeneity of symptoms in different patients. The authors presented a series of cases of patients diagnosed with depression in whom at least one previous antidepressant treatment was shown to be ineffective before drug targeted symptom cluster-matching treatment (SCMT). The presented pilot study shows for the first time the effectiveness of SCMT in the different clusters of depressive symptoms. All the described patients obtained recovery from depressive symptoms after introducing drug-targeted SCMT. Once validated in clinical trials, SCMT might become an effective and rational method of selecting an antidepressant according to the individual profile of depressive symptoms, the mechanism of their formation, and the mechanism of drug action. Although the study results are preliminary, SCMT can be a way to personalize treatment, increasing the likelihood of improvement even in patients who meet criteria for treatment-resistant depression. Full article

(This article belongs to the Special Issue Psychopharmacology of Affective Disorders)

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9 pages, 621 KiB

Open AccessArticle

Withdrawal Symptoms Following Discontinuation of Vortioxetine—Retrospective Chart Review

by Marcin Siwek, Adrian Andrzej Chrobak, Aleksandra Gorostowicz, Anna Julia Krupa and Dominika Dudek

Pharmaceuticals 2021, 14(5), 451; https://doi.org/10.3390/ph14050451 - 11 May 2021

Cited by 7 | Viewed by 4842

Abstract

The efficacy of vortioxetine has been proven in many studies, but data concerning discontinuation symptoms (DS) after vortioxetine withdrawal is scarce. The aim of our study is to systematically evaluate the prevalence, determinants, and clinical features of vortioxetine DS in a retrospective chart [...] Read more.

The efficacy of vortioxetine has been proven in many studies, but data concerning discontinuation symptoms (DS) after vortioxetine withdrawal is scarce. The aim of our study is to systematically evaluate the prevalence, determinants, and clinical features of vortioxetine DS in a retrospective chart review. Data were obtained from medical records of 263 adult patients with depressive disorders who discontinued former vortioxetine treatment. DS were observed in eight (3%) patients after 71–375 days (median 272) of treatment. DS emerged after median three days following vortioxetine withdrawal and lasted for median seven days. The clinical presentation of DS involved: emotional lability (100% of patients), irritability (75%), sudden worsening of mood (75%), nervousness (37.5%), and agitation (37.5%). Median DESS score was four (range of four to six). DS were significantly more prevalent after accidental vs. planned discontinuation (adjusted p = 0.011) and were less frequent after switching to a different antidepressant vs. ceasing pharmacotherapy (adjusted p = 0.0165). DS appeared more often if patients discontinued therapy without medical consultation (adjusted p = 0.033). The occurrence of DS was not associated with the dose and way of drug discontinuation (sudden vs. gradual). In sum, our results show that clinicians should be aware that vortioxetine withdrawal is associated with the possibility of DS. Full article

(This article belongs to the Special Issue Psychopharmacology of Affective Disorders)

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9 pages, 931 KiB

Open AccessArticle

Magnesium in Ketamine Administration in Treatment-Resistant Depression

by Natalia Górska, Wiesław Jerzy Cubała, Jakub Słupski, Mariusz Stanisław Wiglusz, Maria Gałuszko-Węgielnik, Mateusz Kawka and Agata Grzegorzewska

Pharmaceuticals 2021, 14(5), 430; https://doi.org/10.3390/ph14050430 - 3 May 2021

Cited by 1 | Viewed by 4239

Abstract

Relationship between depression and magnesium levels is reported. This observational study examined whether serum magnesium concentration change over time of ketamine treatment course, also whether association between magnesium concentrations and treatment response measured with Montgomery-Åsberg Depression Rating Scale (MADRS) score occurs. Moreover, interlink [...] Read more.

Relationship between depression and magnesium levels is reported. This observational study examined whether serum magnesium concentration change over time of ketamine treatment course, also whether association between magnesium concentrations and treatment response measured with Montgomery-Åsberg Depression Rating Scale (MADRS) score occurs. Moreover, interlink between changes in Young Mania Rating Scale (YMRS) score, somatic comorbidities, and magnesium concentration was studied. Inpatients with major depressive disorder or bipolar disorder were rated weekly by clinician using MADRS and YMRS. Magnesium levels assessments were carried out weekly, before start of ketamine treatment and then every second infusion and one week after last ketamine infusion. The concentration of Mg²⁺ ions differs depending on the measurement. The Mg²⁺ concentration in pre-measurement was significantly higher than in measurement after five infusions (p = 0.031) and after seven infusions (p = 0.003). No significant correlation was observed between changes in magnesium serum levels and MADRS or YMRS. The concentration of Mg²⁺ ion in course of the treatment was not associated with somatic comorbidities. The study supports data for role of magnesium in treatment-resistant depression, particularly related to ketamine treatment, but provides no clear evidence of straightforward association between magnesium serum concentration and treatment response or comorbidity. Full article

(This article belongs to the Special Issue Psychopharmacology of Affective Disorders)

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Review

Jump to: Research, Other

31 pages, 1703 KiB

Open AccessReview

Exploring the Role of Nutraceuticals in Major Depressive Disorder (MDD): Rationale, State of the Art and Future Prospects

by Miguel A. Alvarez-Mon, Miguel A. Ortega, Cielo García-Montero, Oscar Fraile-Martinez, Jorge Monserrat, Guillermo Lahera, Fernando Mora, Alberto Rodriguez-Quiroga, Sonia Fernandez-Rojo, Javier Quintero and Melchor Alvarez-Mon

Pharmaceuticals 2021, 14(8), 821; https://doi.org/10.3390/ph14080821 - 21 Aug 2021

Cited by 24 | Viewed by 7830

Abstract

Major depressive disorder (MDD) is a complex and common disorder, with many factors involved in its onset and development. The clinical management of this condition is frequently based on the use of some pharmacological antidepressant agents, together with psychotherapy and other alternatives in [...] Read more.

Major depressive disorder (MDD) is a complex and common disorder, with many factors involved in its onset and development. The clinical management of this condition is frequently based on the use of some pharmacological antidepressant agents, together with psychotherapy and other alternatives in most severe cases. However, an important percentage of depressed patients fail to respond to the use of conventional therapies. This has created the urgency of finding novel approaches to help in the clinical management of those individuals. Nutraceuticals are natural compounds contained in food with proven benefits either in health promotion or disease prevention and therapy. A growing interest and economical sources are being placed in the development and understanding of multiple nutraceutical products. Here, we summarize some of the most relevant nutraceutical agents evaluated in preclinical and clinical models of depression. In addition, we will also explore less frequent but interest nutraceutical products which are starting to be tested, also evaluating future roads to cover in order to maximize the benefits of nutraceuticals in MDD. Full article

(This article belongs to the Special Issue Psychopharmacology of Affective Disorders)

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11 pages, 557 KiB

Open AccessReview

Lysergic Acid Diethylamide, Psilocybin and Dimethyltryptamine in Depression Treatment: A Systematic Review

by Gniewko Więckiewicz, Iga Stokłosa, Magdalena Piegza, Piotr Gorczyca and Robert Pudlo

Pharmaceuticals 2021, 14(8), 793; https://doi.org/10.3390/ph14080793 - 12 Aug 2021

Cited by 16 | Viewed by 17188

Abstract

Despite many different kinds of substances available for depression treatment, depression itself still appears to be a clinical challenge. Recently, formerly illicit substances came to scientists’ attention, including lysergic acid diethylamide (LSD), psilocybin and dimethyltryptamine (DMT). Some studies suggest that these substances might [...] Read more.

Despite many different kinds of substances available for depression treatment, depression itself still appears to be a clinical challenge. Recently, formerly illicit substances came to scientists’ attention, including lysergic acid diethylamide (LSD), psilocybin and dimethyltryptamine (DMT). Some studies suggest that these substances might be effective in depression treatment. The aim of this study was to evaluate the efficiency of LSD, psilocybin and DMT in depression treatment in the light of current medical literature. The authors followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines for this systematic review. The authors searched the PubMed and Cochrane Library databases to identify relevant publications. Finally, 10 papers were included. Most of the selected studies showed significant correlation between psilocybin and DMT use and reduction in depression symptom intensity. By analyzing qualified studies, it can be concluded that psilocybin and DMT could be useful in depression treatment, but further observations are still required. Full article

(This article belongs to the Special Issue Psychopharmacology of Affective Disorders)

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14 pages, 1189 KiB

Open AccessReview

Possible Antidepressant Effects of Memantine—Systematic Review with a Case Study

by Marek Krzystanek, Stanisław Surma, Artur Pałasz, Monika Romańczyk and Krzysztof Krysta

Pharmaceuticals 2021, 14(5), 481; https://doi.org/10.3390/ph14050481 - 18 May 2021

Cited by 12 | Viewed by 6876

Abstract

The treatment of bipolar depression is hampered by the inadequate efficacy of antidepressants, moderate effect of mood stabilizers, and the side effects of some second-generation antipsychotics. There is limited evidence to date regarding the antidepressant effects of memantine in bipolar depression. The aim [...] Read more.

The treatment of bipolar depression is hampered by the inadequate efficacy of antidepressants, moderate effect of mood stabilizers, and the side effects of some second-generation antipsychotics. There is limited evidence to date regarding the antidepressant effects of memantine in bipolar depression. The aim of the article was to provide a short review of preclinical and clinical studies on the antidepressant effect of memantine, and to present the case of a bipolar depression patient successfully treated with memantine. The described patient with bipolar disorder was unsuccessfully treated with two mood stabilizers. The addition of memantine at a dose of 20 mg/d to the treatment with lamotrigine and valproic acid resulted in a reduction in the severity of depression measured on the HDRS-17 scale by 35%, and by 47.1% after 7 weeks. The discussion presents experimental evidence for the antidepressant effect of memantine, as well as data from clinical trials in recurrent and bipolar depression. The presented case is the second report in the medical literature showing the antidepressant effect of memantine as an add-on treatment for bipolar depression. The described case and literature analysis indicate that memantine may be an effective and safe method of augmentation of mood stabilizing therapy in bipolar depression. Full article

(This article belongs to the Special Issue Psychopharmacology of Affective Disorders)

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19 pages, 391 KiB

Open AccessReview

Probiotics as a Treatment for “Metabolic Depression”? A Rationale for Future Studies

by Oliwia Gawlik-Kotelnicka and Dominik Strzelecki

Pharmaceuticals 2021, 14(4), 384; https://doi.org/10.3390/ph14040384 - 20 Apr 2021

Cited by 12 | Viewed by 4532

Abstract

Depression and metabolic diseases often coexist, having several features in common, e.g., chronic low-grade inflammation and intestinal dysbiosis. Different microbiota interventions have been proposed to be used as a treatment for these disorders. In the paper, we review the efficacy of probiotics in [...] Read more.

Depression and metabolic diseases often coexist, having several features in common, e.g., chronic low-grade inflammation and intestinal dysbiosis. Different microbiota interventions have been proposed to be used as a treatment for these disorders. In the paper, we review the efficacy of probiotics in depressive disorders, obesity, metabolic syndrome and its liver equivalent based on the published experimental studies, clinical trials and meta-analyses. Probiotics seem to be effective in reducing depressive symptoms when administered in addition to antidepressants. Additionally, probiotics intake may ameliorate some of the clinical components of metabolic diseases. However, standardized methodology regarding probiotics use in clinical trials has not been established yet. In this narrative review, we discuss current knowledge on the recently used methodology with its strengths and limitations and propose criteria that may be implemented to create a new study of the effectiveness of probiotics in depressive disorders comorbid with metabolic abnormalities. We put across our choice on type of study population, probiotics genus, strains, dosages and formulations, intervention period, as well as primary and secondary outcome measures. Full article

(This article belongs to the Special Issue Psychopharmacology of Affective Disorders)

Other

Jump to: Research, Review

25 pages, 555 KiB

Open AccessSystematic Review

Adverse Drug Reactions in Relation to Clozapine Plasma Levels: A Systematic Review

by Maria Skokou, Eleni A. Karavia, Zoi Drakou, Vassiliki Konstantinopoulou, Christina-Anna Kavakioti, Philippos Gourzis, Kyriakos E. Kypreos and Ourania Andreopoulou

Pharmaceuticals 2022, 15(7), 817; https://doi.org/10.3390/ph15070817 - 1 Jul 2022

Cited by 23 | Viewed by 4592

Abstract

Clozapine is the gold standard for treatment-resistant schizophrenia. Serious and even life-threatening adverse effects, mostly granulocytopenia, myocarditis, and constipation, are of great clinical concern and constitute a barrier to prescribing clozapine, thus depriving many eligible patients of a lifesaving treatment option. Interestingly, clozapine [...] Read more.

Clozapine is the gold standard for treatment-resistant schizophrenia. Serious and even life-threatening adverse effects, mostly granulocytopenia, myocarditis, and constipation, are of great clinical concern and constitute a barrier to prescribing clozapine, thus depriving many eligible patients of a lifesaving treatment option. Interestingly, clozapine presents variable pharmacokinetics affected by numerous parameters, leading to significant inter- and intra-individual variation. Therefore, therapeutic drug monitoring of plasma clozapine levels confers a significant benefit in everyday clinical practice by increasing the confidence of the prescribing doctor to the drug and the adherence of the patient to the treatment, mainly by ensuring effective treatment and limited dose-related side effects. In the present systematic review, we aimed at identifying how a full range of adverse effects relates to plasma clozapine levels, using the Jadad grading system for assessing the quality of the available clinical evidence. Our findings indicate that EEG slowing, obsessive-compulsive symptoms, heart rate variability, hyperinsulinemia, metabolic syndrome, and constipation correlate to plasma clozapine levels, whereas QTc, myocarditis, sudden death, leucopenia, neutropenia, sialorrhea, are rather unrelated. Rapid dose escalation at the initiation of treatment might contribute to the emergence of myocarditis, or leucopenia. Strategies for managing adverse effects are different in these conditions and are discussed accordingly. Full article

(This article belongs to the Special Issue Psychopharmacology of Affective Disorders)

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22 pages, 1049 KiB

Open AccessSystematic Review

Depression and Autoimmune Hypothyroidism—Their Relationship and the Effects of Treating Psychiatric and Thyroid Disorders on Changes in Clinical and Biochemical Parameters Including BDNF and Other Cytokines—A Systematic Review

by Zofia Kotkowska and Dominik Strzelecki

Pharmaceuticals 2022, 15(4), 391; https://doi.org/10.3390/ph15040391 - 24 Mar 2022

Cited by 10 | Viewed by 8428

Abstract

Various autoimmune diseases, including autoimmune hypothyroidism (AHT), are associated with a higher risk of developing mood disorders throughout life. Depression is accompanied by the changes in the levels of inflammatory and trophic factors, including interleukins (IL-1beta, IL-2, IL-6), interferon alpha (IFN-alpha), tumor necrosis [...] Read more.

Various autoimmune diseases, including autoimmune hypothyroidism (AHT), are associated with a higher risk of developing mood disorders throughout life. Depression is accompanied by the changes in the levels of inflammatory and trophic factors, including interleukins (IL-1beta, IL-2, IL-6), interferon alpha (IFN-alpha), tumor necrosis factor alpha (TNF-alpha), C-reactive protein (CRP), and brain derived neurotrophic factor (BDNF). Disclosure of the relationship between the coexistence of depression and AHT indicates that the pathomechanism of depression may be related to the changes in the immune system, it is also possible that both conditions may be caused by the same immune processes. The above hypothesis is indirectly supported by the observations that the treatment with both antidepressants and levothyroxine leads to a decrease in the levels of proinflammatory cytokines with an increase in BDNF concentrations, simultaneously correlating with an improvement in the clinical parameters. However, so far there are no long-term studies determining the causal relationship between depression, thyroid autoantibodies, and cytokine profile, which could bring us closer to understanding the interrelationships between them and facilitate the use of an adequate pharmacotherapy, not necessarily psychiatric. We consider the above issues to be insufficiently investigated but of great importance. This article is an overview of the available literature as well as an introduction to our research project. Full article

(This article belongs to the Special Issue Psychopharmacology of Affective Disorders)

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19 pages, 3254 KiB

Open AccessSystematic Review

Effect of Psychobiotics on Psychometric Tests and Inflammatory Markers in Major Depressive Disorder: Meta-Analysis of Randomized Controlled Trials with Meta-Regression

by Agata Misera, Paweł Liśkiewicz, Igor Łoniewski, Karolina Skonieczna-Żydecka and Jerzy Samochowiec

Pharmaceuticals 2021, 14(10), 952; https://doi.org/10.3390/ph14100952 - 23 Sep 2021

Cited by 13 | Viewed by 3399

Abstract

Probiotics were shown to act positively on gut–brain axis signaling. We aimed to assess the effect of the administration of a new class of probiotics—psychobiotics—using data from individual psychometric scales, markers of the immune system and neuroactive metabolites. Medical databases were searched from [...] Read more.

Probiotics were shown to act positively on gut–brain axis signaling. We aimed to assess the effect of the administration of a new class of probiotics—psychobiotics—using data from individual psychometric scales, markers of the immune system and neuroactive metabolites. Medical databases were searched from database inception until 22 April 2021 for randomized clinical trials in clinically proven Major Depressive Disorder (MDD) patients treated with either probiotics or placebo reporting any psychometric score (PROSPERO registration number: CRD42021253024). Ten studies with 705 randomized participants and 603 analyzed were included. The mean age of individuals was 38.43 ± 12.1 years, predominantly women (n = 461, 76.45). The mean study duration was 48.8 ± 12.3 (range = 28–62) days. The dosage ranged between 1 × 10⁹ to 2 × 10¹⁰ colony forming units (CFU)/day. We found that probiotics might alleviate symptoms of MDD; endpoint data (pooled scores): SMD = −0.292, 95%CI = −0.577 to −0.007, p < 0.044; change scores (BDI): SMD = −0.482, 95%CI = −0.854 to –0.109, p < 0.011; DM = −4.848, 95%CI = −8.559 to −1.137, p < 0.01. The therapy tended to be more effective with time of psychobiotic supplementation (coefficient = −0.12, SE = 0.06, Z = −1.84, p = 0.06) and in men (% of females: coefficient = 0.1, SE = 0.06, Z = 1.78, p = 0.07). Psychobiotics have great potential in the treatment of MDD. However, no specific strain/strains, dosage or duration of treatment can currently be recommended. Full article

(This article belongs to the Special Issue Psychopharmacology of Affective Disorders)

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15 pages, 662 KiB

Open AccessSystematic Review

A Systematic Review of the Clinical Use of Gabapentin and Pregabalin in Bipolar Disorder

by Qin Xiang Ng, Ming Xuan Han, Seth En Teoh, Clyve Yu Leon Yaow, Yu Liang Lim and Kuan Tsee Chee

Pharmaceuticals 2021, 14(9), 834; https://doi.org/10.3390/ph14090834 - 24 Aug 2021

Cited by 8 | Viewed by 7239

Abstract

Despite its prevalence and disease burden, several chasms still exist with regard to the pharmacotherapy of bipolar disorder (BD). Polypharmacy is commonly encountered as a significant proportion of patients remain symptomatic, and the management of the depressive phase of the illness is a [...] Read more.

Despite its prevalence and disease burden, several chasms still exist with regard to the pharmacotherapy of bipolar disorder (BD). Polypharmacy is commonly encountered as a significant proportion of patients remain symptomatic, and the management of the depressive phase of the illness is a particular challenge. Gabapentin and pregabalin have often been prescribed off-label in spite of a paucity of evidence and clinical practice guidelines to support its use. This systematic review aimed to synthesize the available human clinical trials and inform evidence-based pharmacological approaches to BD management. A total of six randomized, controlled trials (RCTs) and 13 open-label trials involving the use of gabapentin and pregabalin in BD patients were reviewed. Overall, the studies show that gabapentin and its related drug pregabalin do not have significant clinical efficacy as either monotherapy or adjunctive therapy for BD. Gabapentin and pregabalin are probably ineffective for acute mania based on the findings of RCT, with only small open-label trials to support its potential adjunctive role. However, its effects on the long-term outcomes of BD remain to be elucidated. The evidence base was significantly limited by the generally small sample sizes and the trials also had heterogeneous designs and generally high risk of bias. Full article

(This article belongs to the Special Issue Psychopharmacology of Affective Disorders)

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