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Pharmaceuticals
Special Issues
Treatment of Affective Disorders: Adverse Effects, Drug Interactions and Tolerability
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Treatment of Affective Disorders: Adverse Effects, Drug Interactions and Tolerability

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 31020

Special Issue Editor

Dr. Marcin Siwek

E-Mail Website
Guest Editor
Department of Affective Disorders, Chair of Psychiatry, Jagiellonian University Medical College, Kraków, Poland
Interests: treatment of depression, bipolar disorder, and anxiety disorders; coexistence of pain and psychiatric disorders; drug treatment of refractory disorders; drug interactions and side effects; neuropsychiatry

Special Issue Information

Dear Colleagues,

Effective treatment of affective disorders may be challenging. Up to 40% of depressive patients may not achieve satisfactory response to first-line treatment, and in a one-third of them, drug resistance persists after a number of pharmacological interventions, constituting a serious therapeutic issue. The problem  of suboptimal and unsatisfactory treatment outcomes becomes even more complex in bipolar disorder due to the higher incidence of drug resistance and the occurrence of mixed episodes. Therefore, treatment frequently requires the use of a combination of drugs belonging to different medication classes. Simultaneous use of two or more drugs poses the risk of interactions. This results in drug toxicity effects, multiplication of adverse effects, decreased tolerability and, importantly, significant risk of non-compliance, treatment discontinuation or lack of functional remission. Another issue is the high comorbidity of somatic diseases and affective disorders, often resulting in the accumulation of side effects and interactions between psychotropics and non-psychiatric drugs. Thus, contraindications resulting from general medical state should also be taken into account. In this Special Issue, our aim will be to focus on those challenging aspects of the treatment of affective disorders—adverse effects, drug interactions, and tolerability.

Dr. Marcin Siwek
Guest Editor

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • major depression
  • bipolar disorder
  • antidepressants
  • mood stabilizers

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Published Papers (6 papers)

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Research

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10 pages, 672 KiB  
Communication
Amantadine in Treatment of Dysthymia—The Pilot Case Series Study
by Marek Krzystanek, Ewa Martyniak, Artur Pałasz, Katarzyna Skałacka, Artur Chwalba and Piotr Wierzbiński
Pharmaceuticals 2023, 16(6), 897; https://doi.org/10.3390/ph16060897 - 19 Jun 2023
Cited by 2 | Viewed by 6057
Abstract
Dysthymia is a common chronic mood disorder in which isolated symptoms of depression persist for at least 2 years. Despite the many medications recommended for the treatment of dysthymia, no recommendations have yet been made for the treatment of patients who fail to [...] Read more.
Dysthymia is a common chronic mood disorder in which isolated symptoms of depression persist for at least 2 years. Despite the many medications recommended for the treatment of dysthymia, no recommendations have yet been made for the treatment of patients who fail to achieve clinical improvement. This justifies attempts to identify second-line drugs for the treatment of dysthymia. In an open and naturalistic case study, five patients diagnosed with dysthymia in whom at least one antidepressant treatment was ineffective were treated with amantadine. In the age- and gender-matched external control group, patients were treated with sertraline at 100 mg/day. Depressive symptoms were assessed using HDRS-17. Two men and three women were treated with 100 mg amantadine for 3 months with 3–5 months follow-up. After 1 month of treatment with amantadine, a significant reduction in the intensity of depressive symptoms was achieved in all patients, and the clinical improvement increased over the next 2 months of treatment. No deterioration in well-being was observed in any patient after discontinuation of amantadine. The effect of amantadine treatment was comparable to that of sertraline treatment in patients with dysthymia who improved with this drug. The present study indicates that amantadine is an effective and well-tolerated drug in the treatment of dysthymia. Amantadine may be associated with a quick improvement in symptoms in the treatment of dysthymia. Treatment with this drug seems to be associated with good tolerability and persistency of the therapeutic effect after the discontinuation of the treatment. Full article
(This article belongs to the Special Issue Treatment of Affective Disorders: Adverse Effects, Drug Interactions and Tolerability)
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10 pages, 274 KiB  
Article
Safety and Tolerability of the Acute Ketamine Treatment in Treatment-Resistant Depression: Focus on Comorbidities Interplay with Dissociation and Psychomimetic Symptoms
by Adam Włodarczyk, Alicja Dywel and Wiesław Jerzy Cubała
Pharmaceuticals 2023, 16(2), 173; https://doi.org/10.3390/ph16020173 - 24 Jan 2023
Cited by 2 | Viewed by 2532
Abstract
There is evidence for ketamine use in treatment-resistant depression (TRD). Several safety concerns arise regarding adverse drug reactions in specific subpopulations. The aim of this study was to investigate the safety of intravenous ketamine treatment in relation to dissociative and psychotic measures in [...] Read more.
There is evidence for ketamine use in treatment-resistant depression (TRD). Several safety concerns arise regarding adverse drug reactions in specific subpopulations. The aim of this study was to investigate the safety of intravenous ketamine treatment in relation to dissociative and psychotic measures in TRD inpatients with Major Depressive Disorder (MDD) and Bipolar depression (BP) with comorbidities. In total, 49 inpatients with MDD or BP were treated with ketamine following the registered naturalistic observational protocol in a tertiary reference unit for mood disorders (NCT04226963). This dataset represents an intermittent analysis of an observational study performed for interim modeling of observational learning. The observations were applied to the inhomogeneous TRD population in a single site with no blinding and were limited to acute administration. The presence of epilepsy was significantly associated with an elevation in the BPRS over time (p = 0.008). Psychotic symptomatology with BPRS scores for comorbid conditions excluding epilepsy turned out to be insignificant (p = 0.198) regardless of the diagnosis. However, for a subgroup of patients with epilepsy (n = 6), a substantial fluctuation was seen across all administrations in the time course of the study. The study results contribute to the literature on the safety and tolerability profile of CNS adverse drug reactions in short-term treatment with intravenous ketamine as an add-on intervention to current standard-of-care psychotropic medication in TRD-MDD and TRD-BP inpatients with comorbidities. The careful consideration of comorbidities and concomitant medication is needed with ketamine administration along with close-clinical supervision at every visit. Full article
(This article belongs to the Special Issue Treatment of Affective Disorders: Adverse Effects, Drug Interactions and Tolerability)

Review

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30 pages, 689 KiB  
Review
Pharmacological Treatment of Bipolar Depression: A Review of Observational Studies
by Frederike T. Fellendorf, Edoardo Caboni, Pasquale Paribello, Martina Pinna, Ernesto D’Aloja, Sara Carucci, Federica Pinna, Eva Z. Reininghaus, Bernardo Carpiniello and Mirko Manchia
Pharmaceuticals 2023, 16(2), 182; https://doi.org/10.3390/ph16020182 - 25 Jan 2023
Cited by 2 | Viewed by 4700
Abstract
The persistence of depressive morbidity is frequent in bipolar disorder, and the pharmacological management of this symptomatology often lacks effectiveness. This systematic review aimed to summarize the results of the naturalistic observational studies on the pharmacological treatment of bipolar depression published through April [...] Read more.
The persistence of depressive morbidity is frequent in bipolar disorder, and the pharmacological management of this symptomatology often lacks effectiveness. This systematic review aimed to summarize the results of the naturalistic observational studies on the pharmacological treatment of bipolar depression published through April 2022. The certainty of evidence was evaluated according to the GRADE approach. In sum, 16 studies on anticonvulsants, 20 on atypical antipsychotics, 2 on lithium, 28 on antidepressants, and 9 on other compounds were found. Lamotrigine, quetiapine, aripiprazole, and ketamine were the most investigated compounds. Overall, the results support the recommendations regarding the effectiveness of lamotrigine and quetiapine. In contrast to the current recommendations, aripiprazole was shown to be effective and generally well tolerated. Additionally, SSRIs were shown to be effective, but, since they were associated with a possibly higher switch risk, they should be used as an adjunctive therapy to mood stabilizers. Lithium was only studied in two trials but was shown to be effective, although the serum concentrations levels were not associated with clinical response. Finally, ketamine showed divergent response rates with a low certainty of evidence and, so far, unclear long-term effects. Heterogeneity in diagnosis, sample sizes, study designs, reporting of bias, and side effects limited the possibility of a head-to-head comparison. Full article
(This article belongs to the Special Issue Treatment of Affective Disorders: Adverse Effects, Drug Interactions and Tolerability)
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14 pages, 305 KiB  
Review
Long-Term Lithium Therapy: Side Effects and Interactions
by Ewa Ferensztajn-Rochowiak and Janusz K. Rybakowski
Pharmaceuticals 2023, 16(1), 74; https://doi.org/10.3390/ph16010074 - 3 Jan 2023
Cited by 22 | Viewed by 8732
Abstract
Lithium remains the drug of first choice for prophylactic treatment of bipolar disorder, preventing the recurrences of manic and depressive episodes. The longitudinal experiences with lithium administration greatly exceed those with other mood stabilizers. Among the adverse side effects of lithium, renal, gastrointestinal, [...] Read more.
Lithium remains the drug of first choice for prophylactic treatment of bipolar disorder, preventing the recurrences of manic and depressive episodes. The longitudinal experiences with lithium administration greatly exceed those with other mood stabilizers. Among the adverse side effects of lithium, renal, gastrointestinal, neurological, thyroid, metabolic, cognitive, dermatological, cardiologic, and sexual are listed. Probably, the most important negative effect of lithium, occurring mostly after 10–20 years of its administration, is interstitial nephropathy. Beneficial side-effects of long-term lithium therapy also occur such as anti-suicidal, antiviral, and anti-dementia ones. Pharmacokinetic and pharmacodynamic interactions of lithium, mostly those with other drugs, may have an impact on the success of long-term lithium treatment. This paper makes the narrative updated review of lithium-induced side-effects and interactions that may influence its prophylactic effect in bipolar disorder. Their description, mechanisms, and management strategies are provided. The papers appearing in recent years focused mainly on the long-term lithium treatment are reviewed in detail, including recent research performed at Department of Psychiatry, Poznan University of Medical Sciences, Poland. Their own observations on ultra-long lithium treatment of patients with bipolar disorder are also presented. The review can help psychiatrists to perform a successful lithium prophylaxis in bipolar patients. Full article
(This article belongs to the Special Issue Treatment of Affective Disorders: Adverse Effects, Drug Interactions and Tolerability)

Other

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12 pages, 429 KiB  
Systematic Review
Depressive and Other Adverse CNS Effects of Fluoroquinolones
by Piotr Wierzbiński, Joanna Hubska, Michał Henzler, Bartłomiej Kucharski, Rafał Bieś and Marek Krzystanek
Pharmaceuticals 2023, 16(8), 1105; https://doi.org/10.3390/ph16081105 - 4 Aug 2023
Cited by 10 | Viewed by 4359
Abstract
Fluoroquinolones (FQs) are widely used drugs around the world. This is a result of their broad spectrum of antibacterial activity, high bioavailability, and known efficacy. Since they appeared on the market, their prescribing frequency has gradually increased. In 2011, FQs became the third [...] Read more.
Fluoroquinolones (FQs) are widely used drugs around the world. This is a result of their broad spectrum of antibacterial activity, high bioavailability, and known efficacy. Since they appeared on the market, their prescribing frequency has gradually increased. In 2011, FQs became the third most prescribed class of antibiotics in the US. Widespread use of these drugs resulted in an increasing number of reported side effects. In 2016, the FDA warned about significant side effects, including mental disorders in the form of anxiety, psychotic symptoms, insomnia, and depression. Psychiatric adverse reactions to FQs occur with a frequency of 1 to 4.4% and the mechanism of their formation is not entirely clear. It is believed that the antagonistic effect of FQs on the GABA receptor or interaction with the main receptor for the glutamatergic system—NMDA—is responsible for this. The paper is a structured review of 68 selected publications and the latest summary of CNS adverse effects that occur during FQ use. Prescribers should be aware of the risk factors for FQ toxicity, including elderly patients with underlying medical conditions or receiving concomitant medication; however, these adverse events may also occur in other groups of patients. Full article
(This article belongs to the Special Issue Treatment of Affective Disorders: Adverse Effects, Drug Interactions and Tolerability)
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24 pages, 3646 KiB  
Systematic Review
Acetylsalicylic Acid and Mood Disorders: A Systematic Review
by Monika Dominiak, Adam Gędek, Michalina Sikorska, Paweł Mierzejewski, Marcin Wojnar and Anna Z. Antosik-Wójcińska
Pharmaceuticals 2023, 16(1), 67; https://doi.org/10.3390/ph16010067 - 31 Dec 2022
Cited by 7 | Viewed by 3705
Abstract
The effects of acetylsalicylic acid (ASA) on mood disorders (MD) and on inflammatory parameters in preclinical and clinical studies have not yet been comprehensively evaluated. The aim of this study was to systematically summarize the available knowledge on this topic according to PRISMA [...] Read more.
The effects of acetylsalicylic acid (ASA) on mood disorders (MD) and on inflammatory parameters in preclinical and clinical studies have not yet been comprehensively evaluated. The aim of this study was to systematically summarize the available knowledge on this topic according to PRISMA guidelines. Data from preclinical and clinical studies were analyzed, considering the safety and efficacy of ASA in the treatment of MD and the correlation of inflammatory parameters with the effect of ASA treatment. Twenty-one studies were included. Both preclinical and clinical studies found evidence indicating the safety and efficacy of low-dose ASA in the treatment of all types of affective episodes in MD. Observational studies have indicated a reduced risk of all types of affective episodes in chronic low-dose ASA users (HR 0.92, 95% CI: 0.88, 0.95, p < 0.0001). An association between ASA response and inflammatory parameters was found in preclinical studies, but this was not confirmed in clinical trials. Further long-term clinical trials evaluating the safety and efficacy of ASA in recurrent MD, as well as assessing the linkage of ASA treatment with inflammatory phenotype and cytokines, are required. There is also a need for preclinical studies to understand the exact mechanism of action of ASA in MD. Full article
(This article belongs to the Special Issue Treatment of Affective Disorders: Adverse Effects, Drug Interactions and Tolerability)
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