Use Of Tricyclic Antidepressants Research Articles

Decrypting the multifaceted peripheral neuropathy based on molecular pathology and therapeutics: a comprehensive review.

Peripheral neuropathy (PN) is a multifaceted complication characterized by nerve damage due to oxidative stress, inflammatory mediators, and dysregulated metabolic processes. Early PN manifests as sensory changes that develop progressively in a "stocking and glove" pattern. A thorough review of literature has been done to find the molecular pathology, clinical trials that have been conducted to screen the effects of different drugs, current treatments and novel approaches used in PN therapy. Diabetic neuropathy occurs due to altered protein kinase C activity, elevated polyol pathway activity in neurons, and Schwann cells-induced hyperglycemia. Other causes involve chemotherapy exposure, autoimmune ailments, and chronic ethanol intake. Symptomatic treatments for neuropathic pain include use of tricyclic antidepressants, anticonvulsants, and acetyl-L-carnitine. Patients will have new hope if clinicians focus on novel therapies including gene therapy, neuromodulation techniques, and cannabidiol as an alternative to traditional medications, as management is still not ideal.

Blunted sudomotor reactivity in fibromyalgia is associated with levels of depression.

Assessment of sudomotor function by distal electrochemical skin conductance (ESC) can provide an index of peripheral neuropathy. This study explored ESC in fibromyalgia (FM) patients, controlling for tricyclic antidepressant use and body mass index, and its association with the clinical severity of the disease. ESC, clinical symptoms and an index of central pain sensitisation derived from pressure algometry were explored in thirty-three fibromyalgia patients and 33 healthy women. ESC was significantly lower in fibromyalgia patients than healthy participants. About 51% of patients exhibited moderate-to-severe ESC dysfunction, indicative of possible neuropathy. However, ESC was not related to any indicators of clinical severity, nor to algometry. ESC only correlated with depression levels; the group differences in ESC disappeared after controlling for depression. Finally, ESC was asymmetric in the overall sample, with lower values seen in the right hand relative to the left one. The greater prevalence of sudomotor dysfunction in fibromyalgia patients is consistent with the presence of neuropathy in subgroups of patients, and with the basic heterogeneity of the disorder. However, neuropathy does not appear helpful for determining the clinical features of the disorders, or the level of central sensitisation measured by pressure algometry. Future studies including patients with fibromyalgia suffering and not suffering from depression as well as patients with depression but free from chronic pain, are required to identify the role of depression in the observed low ESC levels.

ID: 216904 The Use of Capsaicin for the Treatment of Post-Mastectomy Pain Syndrome

Post-Mastectomy Pain (PMP) Syndrome is defined as pain that develops after breast surgery. Chronic PMP is any pain that lasts for >3 months after the surgical procedure (1). In many patients, PMP is debilitating and results in decreased quality of life and increased opioid consumption (1). PMP can occur either due to injury to nerves or the compression of the lateral and medial pectoral nerves at the site of the pectoralis muscle (2). Symptoms typically consist of burning or shooting pain at the site of the mastectomy. Studies have shown that PMP can occur in up to 25% of women who undergo breast surgery (3). First-line treatment for the condition consists of the use of gabapentin or tricyclic antidepressants (4). We present the case of the use of capsaicin for the treatment of PMP for a patient that has failed conservative treatment options. The mechanism of action for capsaicin has been thought to be related to the concept of defunctionalization in which capsaicin has the ability to attenuate hypersensitivity and result in analgesia (5).

Dry mouth effects from drugs used for depression, anxiety, schizophrenia and bipolar mood disorder in adults: systematic review.

Poor oral health is increasingly recognised as an important comorbidity in people with psychiatric illness. One risk factor is psychotropic-induced dry mouth. To perform a systematic review of the severity of dry mouth due to psychotropic drugs in adults (CRD42021239725). Study quality was assessed using the Cochrane risk of bias tool. We searched the following databases: PubMed, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, CINAHL and Web of Science. We included randomised controlled trials (RCTs) measuring the severity of drug-induced hyposalivation and xerostomia. Eighteen RCTs with 605 participants were included. Severity of drug-induced dry mouth was compared among eight drug classes and/or against placebo. All studies were published 20 to 40 years ago and included tricyclic antidepressants (TCAs), serotonin specific reuptake inhibitors (SSRIs) and other drug classes. Meta-analysis was not feasible owing to design heterogeneity. TCAs caused more severe dry mouth, both objectively and subjectively, than placebo or other drug classes. SSRIs were generally associated with less severe symptoms. However, there was no information on antipsychotics or more recently available antidepressants, and there was minimal information on mood stabilisers. Most studies were on healthy subjects, limiting the generalisability of findings. Only one study measured both objective and subjective dry mouth, which have different clinical implications. Psychotropic-induced dry mouth is a poorly researched area, and well-designed RCTs of newer psychotropic drugs using standardised objective and subjective measures are indicated. Given the ongoing use of TCAs for treatment-resistant depression, prescribers need to remain vigilant for xerostomia.

Impact of depression and antidepressant use on clinical outcomes of hepatitis B and C: a population-based study.

Depression is common in patients with chronic viral hepatitis. We evaluated the impact of major depressive disorder (MDD) and antidepressant use on survival among patients with HBV and HCV. We used The Health Improvement Network database, the largest medical database in the UK, to identify incident HBV (n=1401) and HCV (n=1635) in patients between 1986 and 2017. Our primary composite outcome was the development of decompensated cirrhosis or death. MDD and each class of antidepressants were assessed in multivariate Cox proportional hazards models. Models were adjusted for age, sex, and clinical comorbidities. The prevalence of MDD among HCV patients was higher compared with HBV patients (23.5% vs. 9.0%, p<0.001, respectively). Similarly, HCV patients were more likely to use antidepressants (59.6%) compared with HBV patients (27.1%), p>0.001. MDD was not an independent predictor for decompensated cirrhosis-free survival or mortality. However, the use of tricyclic and tetracyclic antidepressants (TCAs) was associated with poor decompensated cirrhosis-free survival in HBV and HCV cohorts (adjusted HR: 1.80, 95% CI, 1.00-3.26 and 1.56, 95% CI, 1.13-2.14, respectively). Both TCAs in the HBV cohort and selective serotonin reuptake inhibitors among the HCV cohort were associated with poor overall survival (adjusted HR: 2.18, 95% CI, 1.16-4.10; 1.48, 95% CI, 1.02-2.16, respectively). Although prevalent among viral hepatitis patients, MDD did not affect disease progression or survival in either HBV or HCV cohorts. TCA use was associated with poor decompensated cirrhosis-free survival. Therefore, its use should be further studied among viral hepatitis patients.

Tricyclic Antidepressants in Nociceptive and Neuropathic Pain: A Review of Their Analgesic Properties in Combination With Opioids.

Objectives: To determine the efficacy and safety of commonly prescribed tricyclic antidepressants (TCAs) as analgesics for nociceptive and neuropathic pain in combination with opioids. Data Sources: A comprehensive literature review was conducted with the assistance of a medical reference librarian on PubMed, MEDLINE, Scopus, and Web of Science using the following search terminology: "Amitriptyline" OR "Doxepin" OR "Desipramine" OR "Imipramine" OR "Nortriptyline" OR "Clomipramine" OR "Trimipramine" AND "Analgesia." Reports of adult patients who received any TCA as an adjunctive analgesic to opioids were included. Study Selection and Data Extraction: A total of 293 results were obtained from the initial database inquiries, following which exclusion criteria were applied and 6 articles were included in this review. Three of the reports detailed the use of TCAs in the perioperative setting, whereas the remaining 3 evaluated their effect on different etiologies of neuropathic pain. Data Synthesis: Tricyclic antidepressants were found to have modest, yet not insignificant, independent analgesic properties, although the ability to provide pain relief was relegated to a select few agents. Desipramine has the most data available for use in nociceptive, postoperative pain through its ability to potentiate and prolong the analgesic effects of opioids and was not associated with adverse drug effects. Conclusions: The efficacy of TCAs for neuropathic pain was not corroborated by this review, and the anticholinergic adverse effects associated with this drug class were found to be significant. Further research is needed to quantify the efficacy of TCAs in the management of nociceptive pain.

Risk of cardiovascular events according to the tricyclic antidepressant dosage in patients with chronic pain: a retrospective cohort study.

We aimed to examine the risk of cardiovascular adverse events by tricyclic antidepressant (TCA) dosage among patients with chronic pain. A retrospective cohort study was conducted using a nationwide sample cohort. Among patients aged ≥ 18years with a chronic pain diagnosis and no history of cardiovascular events, we extracted users and non-users of TCAs through 1:1 propensity score matching. TCA users were categorized into three groups according to the mean defined daily dose (DDD): very low doses (< 0.15 DDD), low doses (0.15-0.34 DDD), and traditional doses (≥ 0.34 DDD). A 6-month follow-up was conducted with an intention-to-treat approach. We examined the hazard ratio of cardiovascular adverse events using Cox proportional hazards analysis. In total, 16,660 matched patients were followed up (8330 TCA users and 8330 non-users). TCA use did not significantly increase cardiovascular adverse events (hazard ratio [HR] 1.12, 95% confidence interval [CI] 0.94-1.33). Low-dose (0.15-0.34 DDD) TCAs (HR 1.37, 95% CI 1.08-1.74), particularly low-dose (0.15-0.34 DDD) nortriptyline (HR 2.11, 95% CI 1.44-3.08), was associated with an increased risk of cardiovascular adverse events. Administration of TCAs at the traditional dose (≥ 0.34 DDD) increased the risk of ischemic stroke (HR 2.08, 95% CI 1.11-3.88). Close monitoring of patients on long-term, low-dose use of TCAs should be conducted to avoid an increase in the cumulative dose, which increases the risk of cardiovascular adverse events.

The use of antidepressants is linked to bone loss: A systematic review and metanalysis.

Depression and antidepressants are among risk factors for osteoporosis. However, there are still inconsistencies in literature regarding bone consequences of antidepressant drugs and the role of age and the natural decline of bone health in patients with depression. To investigate the relationship between antidepressant and bone mineral density (BMD). We conducted a systematic review and metanalysis according to PRISMA guidelines searching on PubMed/Medline, Cochrane Database, and Scopus libraries and registered with PROSPERO (registration number CRD42021254006) using generic terms for antidepressants and BMD. Search was restricted to English language only and without time restriction from inception up to June 2021. Methodological quality was assessed with the Newcastle-Ottawa scale. Eighteen papers were included in the qualitative analysis and five in the quantitative analysis. A total of 42,656 participants affected by different subtypes of depression were identified. Among the included studies, 10 used serotonin reuptake inhibitors (SSRIs) only, 6 involved the use of SSRIs and tricyclic antidepressants, and 2 the combined use of more than two antidepressants. No significant studies meeting the inclusion criteria for other most recent categories of antidepressants, such as vortioxetine and esketamine. Overall, we observed a significant effect of SSRI on decrease of BMD with a mean effect of 0.28 (95% CI = 0.08, 0.39). Our data suggest that SSRIs are associated with a decrease of BMD. We aim to raise clinicians' awareness of the potential association between the use of antidepressants and bone fragility to increase monitoring of bone health.

PAROXETINE OVERDOSE LEADING TO SEROTONIN SYNDROME

PAROXETINE OVERDOSE LEADING TO SEROTONIN SYNDROME

35226 Characterization of pain in prurigo nodularis: An online survey-based study

Background: Prurigo nodularis (PN) is a chronic dermatosis characterized by intense pruritus. While itch in PN is well-characterized, there remains limited understanding of the experience of itch-related pain and patient-reported treatments. Methods: An anonymous online Qualtrics survey was developed and delivered to three international PN support groups from July to September 2021. The survey characterized patient-reported treatments for pain and used validated metrics to assess the severity of symptoms including the Douleur Neuropathique 4i questionnaire (DN4i), Short-form McGill Pain Questionnaire (SF-MPQ-2) and Worst Pain Numeric Rating Scale (WP-NRS). Results: A total of 94 patients completed the survey and met inclusion criteria. Approximately 89.4% of respondents were female with a mean (SD) age of 53.7 (12.9) years. PN-associated pain was a consistently reported symptom with 48.9% of respondents experiencing daily pain. The pain experienced by patients was also classified as moderate-to-severe based on the mean WP-NRS score (6.9 ± 2.6). To assess dimensions of pain, the DN4i and SF-MPQ-2 were used with the majority of respondents (53.2%) meeting criteria for neuropathic pain syndrome based on the DN4i. The mean SF-MPQ-2 score was 2.9 ± 2.2 with the mean neuropathic subscale score of 3.6 ± 1.8. Despite the prevalence of neuropathic pain, only 36.2% of respondents reported lifetime use of gabapentin, pregabalin or tricyclic antidepressants. Conclusions: Moderate-to-severe neuropathic pain is frequently experienced in PN patients. However, the use of medications to address these symptoms is limited. Greater awareness of itch-associated symptoms and medications aimed at alleviating such symptoms may improve quality of life in this patient population.

Risk of Falls Associated with Long-Acting Benzodiazepines or Tricyclic Antidepressants Use in Community-Dwelling Older Adults: A Nationwide Population-Based Case-Crossover Study.

Background: Falls are common in older adults and increase in recent years. This study aimed to examine the risk of falls associated with long-acting benzodiazepines (BZDs) or tricyclic antidepressants (TCAs) use in community-dwelling older adults. Methods: A nationwide population-based case–crossover design was used. We screened information on 6,370,275 fall or fall fracture cases among community-dwelling elderly patients from the database of the national health insurance data warehouse in South Korea. We extracted the data of elderly patients who visited the hospital for a fall and were diagnosed with the first fall or fall fracture after prescription of long-acting BZDs (n = 1805) or TCAs (n = 554). The study used conditional logistic regression analysis to analyze the associations and stratified analysis by gender and age group to control for their confounding effects. Results: Risk of falls or fall fractures increased by more than two times after taking long-acting BZDs (odds ratio [OR] = 2.16; 95% confidence interval [CI] = 1.85–2.52) or TCAs (OR = 2.13; 95% CI = 1.62–2.83). The longer the prescription period of both, the higher the risk of falls or fall fractures was (≥49 days for long-acting BZDs vs. ≥ 56 days for TCAs). Conclusions: Long-acting BZDs or TCAs should be avoided or prescribed for a shorter duration based on these adverse effects. Health care providers should focus on fall prevention practices in older adults who take such drugs.

Antidepressant medication and risk of cardiovascular disease in posttraumatic stress disorder patients: application of marginal structural models in Korean National Health Insurance Database

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): - National Research Foundation of Korea (NRF) grant funded by the Ministry of Science and ICT Introduction Previous evidence on antidepressant medication and cardiovascular disease (CVD) in posttraumatic stress disorder (PTSD) patients is mixed. We evaluated associations between antidepressant medication and CVD by applying marginal structural model. Methods We gathered medical utilization records of 27,170 patients diagnosed with PTSD in years 2004 - 2018 without prior CVD diagnosis from Korean National Health Insurance Database (NHID). PTSD and CVD were characterized in correspondence of ICD-10 diagnostic codes. We acquired information on antidepressant use from medical utilization records and categorized by medication category: selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs) and tricyclic antidepressants (TCAs). Discrete-time survival analysis with marginal structural inverse probability weighting was used to test association between antidepressants and CVDs and were compared to results from traditional time-fixed model and simple time-varying model. We calculated cumulative daily defined doses (DDDs) of each antidepressant categories and conducted polynomial splining to test dose response. Results SSRI use was associated with acute coronary syndrome (hazard ratio [HR] 1.53, 95% confidence interval [CI] 1.26 - 1.86) and ischemic stroke (HR 1.33, 95% CI 1.08 - 1.63). SNRI use was associated with acute coronary syndrome (HR 1.52, 95% CI 1.09 - 2.12). TCA use was associated with acute coronary syndrome (HR 1.54, 1.21 - 1.96) and ischemic stroke (HR 1.34, 1.06 - 1.70). Polynomial spline showed positive dose-response in association between antidepressant use and CVD. Conclusion Antidepressant use is causally associated with CVD in patients with PTSD. Higher cumulative DDD of antidepressant increases the risk of CVD.

Antitumoral Effects of Tricyclic Antidepressants: Beyond Neuropathic Pain Treatment.

Simple SummaryTricyclic antidepressants (TCAs) are old and known therapeutic agents whose good safety profile makes them good candidates for drug repurposing. As the relevance of nerves in cancer development and progression is being unveiled, attention now turns to the use of nerve-targeting drugs, such as TCAs, as an interesting approach to combat cancer. In this review, we discuss current evidence about the safety of TCAs, their application to treat neuropathic pain in cancer patients, and in vitro and in vivo demonstrations of the antitumoral effects of TCAs. Finally, the results of ongoing clinical trials and future directions are discussed.Growing evidence shows that nerves play an active role in cancer development and progression by altering crucial molecular pathways and cell functions. Conversely, the use of neurotropic drugs, such as tricyclic antidepressants (TCAs), may modulate these molecular signals with a therapeutic purpose based on a direct antitumoral effect and beyond the TCA use to treat neuropathic pain in oncology patients. In this review, we discuss the TCAs’ safety and their central effects against neuropathic pain in cancer, and the antitumoral effects of TCAs in in vitro and preclinical studies, as well as in the clinical setting. The current evidence points out that TCAs are safe and beneficial to treat neuropathic pain associated with cancer and chemotherapy, and they block different molecular pathways used by cancer cells from different locations for tumor growth and promotion. Likewise, ongoing clinical trials evaluating the antineoplastic effects of TCAs are discussed. TCAs are very biologically active compounds, and their repurposing as antitumoral drugs is a promising and straightforward approach to treat specific cancer subtypes and to further define their molecular targets, as well as an interesting starting point to design analogues with increased antitumoral activity.

Pharmacological Management of Nightmares Associated with Posttraumatic Stress Disorder.

Posttraumatic stress disorder (PTSD) can be a chronic and disabling condition. Post-traumatic nightmares (PTNs) form a core component of PTSD and are highly prevalent in this patient population. Nightmares in PTSD have been associated with significant distress, functional impairment, poor health outcomes, and decreased quality of life. Nightmares in PTSD are also an independent risk factor for suicide. Nightmare cessation can lead to improved quality of life, fewer hospital admissions, lower healthcare costs, and reduced all-cause mortality. Effective treatment of nightmares is critical and often leads to improvement of other PTSD symptomatology. However, approved pharmacological agents for the treatment of PTSD have modest effects on sleep and nightmares, and may cause adverse effects. No pharmacological agent has been approved specifically for the treatment of PTNs, but multiple agents have been studied. This current narrative review aimed to critically appraise proven as well as novel pharmacological agents used in the treatment of PTNs. Evidence of varying quality exists for the use of prazosin, doxazosin, clonidine, tricyclic antidepressants, trazodone, mirtazapine, atypical antipsychotics (especially risperidone, olanzapine and quetiapine), gabapentin, topiramate, and cyproheptadine. Evidence does not support the use of venlafaxine, β-blockers, benzodiazepines, or sedative hypnotics. Novel agents such as ramelteon, cannabinoids, ketamine, psychedelic agents, and trihexyphenidyl have shown promising results. Large randomized controlled trials (RCTs) are needed to evaluate the use of these novel agents. Future research directions are identified to optimize the treatment of nightmares in patients with PTSD.

Use of Tricyclic Antidepressants in Trigeminal Neuralgia

Use of Tricyclic Antidepressants in Trigeminal Neuralgia

Antidepressants Usage and Risk of Pneumonia Among Elderly Patients With the Parkinson's Disease: A Population-Based Case-Control Study.

The patients with Parkinson's disease (PD) are associated with a higher risk of pneumonia. Antidepressants exert an anticholinergic effect in varying degrees and various classes of antidepressants also can produce a different effect on immune function. The relationship between the risk of pneumonia and the use of antidepressants among elderly patients with PD is unknown. The study investigated the risk of pneumonia associated with the use of antidepressants in elderly patients with PD. This case-control study was based on data from the longitudinal health insurance database in Taiwan. We analyzed the data of 551,975 elderly patients with PD between 2002 and 2018. To reduce the potential confounding caused by unbalanced covariates in non-experimental settings, we used propensity score matching to include older patients without pneumonia to serve as the comparison. The antidepressants in the study included tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), serotonin, and norepinephrine reuptake inhibitors (SNRIs). The conditional logistic regression was used to investigate the association between antidepressants and pneumonia. Control variables in the study included sex, age, income level, urbanization, Charlson comorbidity index score, and comorbidities related to pneumonia. In terms of TCAs users, compared with patients not receiving TCAs, current users had a lower risk of incident pneumonia (adjusted odds ratio [aOR] = 0.86, 95% CI = 0.82–0.90) and recent users (aOR = 0.83, 95% CI = 0.80–0.87). In terms of MAOIs users, current users had a lower risk of incident pneumonia (aOR = 0.88, 95% CI = 0.83–0.93), recent users (aOR = 0.89, 95% CI = 0.85–0.93). In terms of SSRIs users, current users had a higher risk of incident pneumonia (a OR = 1.13, 95% CI = 1.01–1.17), recent users (aOR = 1.01, 95% CI = 1.06–1.13), and past users (aOR = 1.19, 95% CI = 1.17–1.21). In terms of SNRIs users, past users had a higher risk of incident pneumonia (aOR = 1.07, 95% CI = 1.03–1.10). The incident pneumonia is associated with the use of individuals of different classes of antidepressants. The use of TCAs (such as, amitriptyline and imipramine) had a lower odds of incident pneumonia. The use of MAOIs (such as, selegiline and rasagiline) had a lower odds of pneumonia during recent use. The use of SSRIs (such as, fluoxetine, sertraline, escitalopram, paroxetine, and citalopram) and SNRIs (such as, milnacipran, and venlafaxine) had a higher odds of incident pneumonia.

Association of Periodic Limb Movements With Medication Classes: A Retrospective Cohort Study.

To investigate the association between various medication classes and the periodic limb movement index (PLMI) in a clinical cohort of adults who completed in-laboratory polysomnography. A single, diagnostic, overnight, in-laboratory polysomnogram was completed for 3,488 patients consecutively referred from 2010 to 2015 to determine PLMI. Medication use and medical comorbidities were collected through patient questionnaires. Associations between medication classes and PLMI were ascertained using multivariable ordinal logistic regression models. The median age of the cohort was 56.0 years (48.2% male). After adjusting for age, sex, body mass index, relevant comorbidities, and sleep measures, the use of selective serotonin reuptake inhibitors (SSRIs) (odds ratio [OR] 1.52) and serotonin-norepinephrine reuptake inhibitors (SNRIs) (OR 1.99) was associated with increased PLMI. Conversely, gabapentinoids (OR 0.71), stimulants (OR 0.52), benzodiazepines (OR 0.79), and dopamine agonists (OR 0.38) were associated with decreased PLMI. A non-statistically significant trend for decreased PLMI with neuroleptic use was observed. No significant associations were found between PLMI and the use of antihypertensives, statins, tricyclic antidepressants, bupropion, anticoagulants, antiplatelets, modafinil, and antihistamines. The use of SSRIs and SNRIs was associated with elevated PLMI while the use of gabapentinoids, stimulants, benzodiazepines, and dopamine agonists was associated with decreased PLMI. These results can assist physicians in managing periodic limb movements in sleep (PLMS) and invite further research into the relationship between PLMS and medications with the modulating effects of dose, formulation type, and time of administration. This study provides Class II evidence that SSRIs and SNRIs are associated with elevated PLMI while gabapentinoids, stimulants, benzodiazepines, and dopamine agonists are associated with decreased PLMI.

Antidepressant use during pregnancy and gestational diabetes: a systematic review

A high number of women are exposed to antidepressants during pregnancy. Considering that an association between exposure to antidepressants and type 2 diabetes was found in the general population and pregnant women are inherently susceptible to insulin resistance, this study aimed to investigate data in the scientific literature on the association between antidepressant use during pregnancy and the risk of developing gestational diabetes mellitus (GDM). This systematic review was conducted according to the PRISMA guidelines. PubMed, Virtual Health Library (VHS), and Web of Science databases were searched to identify observational studies reporting the association between antidepressant use during pregnancy and GDM. Review articles, case reports, case series, clinical trials, and animal studies were excluded. In total, 67 studies were retrieved, of which 3 were included in the systematic review: one case-control and two cohort studies. According to the Newcastle-Ottawa Scale, the three studies were considered high-quality. Through this systematic review, selective serotonin reuptake inhibitors (SSRI) use during pregnancy is not significantly associated with a higher risk of developing GDM. There are still controversies about the association between serotonin and norepinephrine reuptake inhibitors (SNRI) and GDM. The use of tricyclic, tetracyclic, and atypical antidepressants by pregnant women appears to be associated with GDM. Therefore, the available information about the topic is scarce and the condition of further studies is needed.

Possibilities and limitations of antidepressant use to correct depressive and negative symptoms in schizophrenia

The purpose of this review is to analyze approaches to the treatment of depressive and negative disorders in schizophrenia in terms of their level of efficacy and safety. Materials and Methods: A search was conducted for full-text articles published over the last 10 years in PubMed, Springer, Wiley Online Library, Taylor &amp; Francis Online, APA PsycInfo, CORE, Science Direct, and eLIBRARY.RU databases. Several articles published previously to this period were also included into the review due to their high scientific value. Results: Our review suggests that antidepressants (ADs) are effective medications and they can be prescribed to correct depressive disorders and negative symptoms in patients with schizophrenia when used in combination with antipsychotics (АPs). However, when administering ADs and АPs combinations, it is important to consider the safety profile of these combinations as well as their tolerance. Negative symptoms of schizophrenia, including those induced by a number of АP, are less amenable to correction by АDs monotherapy, which requires a long period of АPs (on average - 8 weeks), which can be limited in the real life of the patient outside the hospital. Current approaches to the therapy of depressive disorders in patients suffering from schizophrenia vary from country to country. However, most of АDs used in clinical psychiatric practice are widely used in the comorbid state under consideration. Conclusion: The efficacy and safety of АDs of the different classes considered in this review depends on their mechanisms of action, duration of admission, type of АPs taken, and specific clinical situation (acute depressive disorder, major depressive episode, or chronic depressive episode). Most promising in clinical practice are serotonin–norepinephrine reuptake inhibitors (SNRIs) and dual ADs. The use of tricyclic antidepressants (TCAs) is limited due to a higher risk of adverse drug reactions (ADRs). The use of most selective serotonin reuptake inhibitors (SSRIs) is limited due to the risk of aggravation of hallucinations (this risk being higher for patients with visual hallucinations, and lower for those with auditory hallucinations) and\or iatrogenic psychosis. These ADRs may probably occur in patients suffering from schizophrenia due to their ideal "poor metabolizer" pharmacogenetic profile, since most of the drugs considered in this review have hepatic metabolism.

Tricyclic antidepressants for major depressive disorder: a comprehensive evaluation of current practice in the Netherlands

BackgroundTraditionally tricyclic antidepressants (TCAs) have an important place in treatment of major depressive disorder (MDD). Today, often other antidepressant medications are considered as first step in the pharmacological treatment of MDD, mainly because they are associated with less adverse effects, whereby the position of TCAs appears unclear. In this study we aimed to examine the current practice of TCAs in treatment of unipolar MDD.MethodsA mixed methods approach was applied. First, a selection of leading international and national guidelines was reviewed. Second, actual TCA prescription was examined by analyzing health records of 75 MDD patients treated with the TCAs nortriptyline, clomipramine or imipramine in different centers in the Netherlands. Third, promotors and barriers influencing the choice for TCAs and dosing strategies were explored using semi-structured interviews with 24 Dutch psychiatrists.ResultsClinical practice guidelines were sometimes indirective and inconsistent with each other. Health records revealed that most patients (71%) attained therapeutic plasma concentrations within two months of TCA use. Patients who achieved therapeutic plasma concentrations reached them on average after 19.6 days (SD 10.9). Both health records and interviews indicated that therapeutic nortriptyline concentrations were attained faster compared to other TCAs. Various factors were identified influencing the choice for TCAs and dosing by psychiatrists.ConclusionsGuideline recommendations and clinical practice regarding TCA prescription for MDD vary. To increase consistency in clinical practice we recommend development of an up-to-date guideline integrating selection and dosing of TCAs, including the roles of therapeutic drug monitoring and pharmacogenetics. Such a guideline is currently lacking and would contribute to optimal TCA treatment, whereby efficacy and tolerability may be increased.