Concurrent Use Of Antidepressants Research Articles

Impact of antidepressant medication on the analgetic effect of repetitive transcranial magnetic stimulation treatment of neuropathic pain. Preliminary findings from a registry study.

Repetitive transcranial magnetic stimulation (rTMS) has been found to be effective in chronic neuropathic pain conditions. However, information about the combined effects of rTMS and antidepressant treatment is scarce. We studied the outcome of rTMS and concurrent antidepressant treatment in patients with neuropathic pain. In this retrospective, real-world study, 34 patients with neuropathic pain, who were considered resistant or not benefitting from conventional treatment, received rTMS treatment between 2017 and 2020. Pain-related factors were measured using the Numerical Rating Scale (NRS), Global Impression of Change (GIC), and Beck Depression Inventory. A decrease in pain intensity and pain interference assessed with NRS was observed after 10 treatment sessions in 16 patients. The impression of change was positive in 20 patients. Half of the patients (n=17) used antidepressant medication, while half (n=17) did not. A concurrent use of antidepressants with therapeutic rTMS was significantly linked with less pain intensity relief when compared with the nonuse of antidepressants (p=0.019). The impression of change was significantly in favor of the antidepressant nonuser group (p=0.002). No group differences in pain interference were found between the groups. Therapeutic rTMS for neuropathic pain is plausibly sensitive to interference with antidepressant medication. The exact mechanism of our findings remains to be elucidated; confirmatory studies are warranted.

Gabapentin utilization among older adults with different cognitive status: Results from the National Alzheimer’s Coordinating Center database (2006‐2019)

AbstractBackgroundAlthough gabapentin use has been increasing among older adults, its safety is understudied. We aimed to examine gabapentin utilization trends among older adults with different cognitive status and investigate potentially inappropriate concurrent medication use with gabapentin.MethodsData were extracted from National Alzheimer’s Coordinating Center Uniform Data Set (2006‐2019). We included participants (age 65+) with any medications reported at the time of visit. Within each study year, we estimated the prevalence of gabapentin use among the participants at each visit, both overall and within subgroups defined by cognitive status [normal, mild cognitive impairment, and dementia] and demographics [age and sex]. Additionally, we assessed prevalence of concurrent use of gabapentin with Central Nervous System (CNS) depressants, including opioid, combined opioid and benzodiazepine, antidepressant, and antipsychotic.ResultsOverall, participant‐reported gabapentin use nearly tripled (2.2 to 6.1%) from 2006 to 2019. Further, prevalence increased over this period in every participant subgroup. Among gabapentin users, the concurrent use of antidepressants or antipsychotics was more common in participants with a dementia diagnosis than those with normal cognition. Over half of gabapentin users with dementia also reported use of antidepressants. The concurrent use of gabapentin with opioids ranged from 10 to 30%, and the concurrent use of gabapentin, benzodiazepine, and opioids was below 8% throughout the study period.ConclusionsGiven increasing use among older adults, including those with cognitive impairment and dementia, rigorous studies are needed to examine the safety of gabapentin in this population, especially when using gabapentin with other CNS medications concurrently.

SSRI potentiation of methadone cardiotoxicity

Methadone maintenance therapy, commonly used in the treatment of opioid use disorder, has been associated with electrocardiographic QT interval prolongation.1 With comorbid mental illness often seen in methadone‐treated patients,2 concurrent antidepressant use is likely. This results in a high potential for drug interaction, especially with selective serotonin reuptake inhibitors (SSRIs).

An audit on prescribing practice and risk of serotonin syndrome among patients with chronic pain

AimsTo determine the incidence of prescribing practice with associated risk of serotonin toxicity among patients with chronic pain conditions.BackgroundSerotonin syndrome is a potentially life-threatening condition caused by excessive serotonergic activity, usually from drug interactions. Concurrent use of antidepressants is strongly linked to serotonin syndrome, with recent data revealing record numbers of NHS prescribed antidepressants in 2019. Antidepressant medications are also used in chronic pain management for their anti-neuropathic pain properties. However, it is well-recognised that a significant number of chronic pain patients suffer from anxiety and depression. This cohort of patients is therefore vulnerable to being exposed to multiple concurrent antidepressant agents, and thus at relatively higher risk of serotonin syndrome compared to other patient groups. Additionally, these patients are likely to be exposed to the concurrent use of antidepressants and certain analgesic agents particularly phenylpiperidine derivatives which increases serotonin toxicity risk.MethodMedications of patients presenting to a secondary care pain clinic within the last year were looked into. Patients were selected at random by pain management secretaries. Concurrent use of multiple antidepressant agents including Selective Serotonin Reuptake Inhibitors (SSRIs), Serotonin Noradrenaline Reuptake Inhibitors (SNRIs), Tricyclic Antidepressants (TCAs) or Tetracyclic Antidepressant (TeCA) was noted. Additionally, concurrent use of any of these antidepressant agents and phenylpiperidine derivatives such as Fentanyl and Tramadol was noted.ResultData on medications of 97 patients were collected. A total of 28 patients (28.8%) were observed to have at-risk medication combinations. Out of these, five patients were on both SSRI and TCA. Two patients were on both TCA and TeCA. Four other patients were on either a combination of SSRI and SNRI, SNRI and TCA, SSRI and TeCA, or TCA and TCA. Three patients were on both Fentanyl patches and an antidepressant. Fourteen patients were on both an antidepressant and Tramadol. None of these patients were diagnosed with serotonin syndrome; however, it is unclear as to whether these patients experienced milder symptoms of the syndrome.ConclusionA considerable number of patients in this group were on medication combinations putting them at risk of serotonin syndrome. Despite no documented patient harm, there is an urgent need for an increased awareness among prescribers on drug interactions which may lead to this syndrome and a subsequent change in prescribing practice.

Associations between statin use and suicidality, depression, anxiety, and seizures: a Swedish total-population cohort study

SummaryBackgroundStatins have shown both protective and adverse associations with neuropsychiatric outcomes. We aimed to examine the possible associations between statins and suicidality, depression, anxiety, and seizures.MethodsUsing Swedish national registers, we linked data on dispensed statin prescriptions with data on unplanned (emergency) hospital visits or specialised outpatient care for four neuropsychiatric outcomes: suicidal behaviour (including deaths from suicide), depressive disorders, anxiety disorders, and seizures. We included all individuals in the registries who were dispensed statins and who were aged 15 years or older between Jan 1, 2006, and Dec 31, 2013. We applied a within-individual design using stratified Cox proportional hazards regression to compare the incidence of the defined outcomes during periods on statins and periods off statins within each individual, thus adjusting for time-invariant confounders. Non-specific effects of treatment were tested by investigating these outcomes in relation to thiazide diuretic use and antihistamine use in the same cohort.FindingsThe statin-users cohort comprised 1 149 384 individuals, of whom 1 015 949 (88·4%) were aged 50 years or older, 625 616 (54·4%) were male, and 523 768 (45·6%) were female. The study period consisted of 2 053 310 non-treatment periods and 2 997 545 treatment periods, and 957 216 (83·3%) individuals had a medication status change (from on statins to off statins, or vice versa). Suicide outcomes were found in 6372 (0·6%) individuals, depressive disorders in 23 745 (2·1%), anxiety disorders in 30 100 (2·6%), and seizures in 28 844 (2·5%). There were no clear associations between periods of statin treatment and suicidal behaviour or deaths from suicide (hazard ratio 0·99 [95% CI 0·90–1·08]), anxiety disorders (0·99 [0·95–1·02]), or seizures (1·00 [0·97–1·04]). Statins were associated with reduced hazards of depressive disorders (0·91 [0·87–0·94]), which remained after adjustment for concurrent antidepressant use (0·91 [0·88–0·94]). Hazard ratios for depressive disorders were 0·61 (0·38–1·00; n=14 718) with thiazide diuretic use and 0·84 (0·67–1·06; n=23 715) with antihistamine use.InterpretationStatin use is not associated with suicidality, anxiety disorders, or seizures. Whether the observed association between statin use and reduced diagnoses of clinical depression is confounded by non-specific benefits related to being prescribed medication needs further research.FundingWellcome Trust, Swedish Research Council, National Institute for Health Research (NIHR) Research Professorship, NIHR Oxford Health Biomedical Research Centre, American Foundation for Suicide Prevention, Karolinska Institutet.

S93. Concurrent Antidepressant Use is Not Associated with Different rTMS Treatment Outcomes for Major Depressive Disorder in a Sham-Controlled Trial

S93. Concurrent Antidepressant Use is Not Associated with Different rTMS Treatment Outcomes for Major Depressive Disorder in a Sham-Controlled Trial

D-Cycloserine Augmentation of Exposure-Based Cognitive Behavior Therapy for Anxiety, Obsessive-Compulsive, and Posttraumatic Stress Disorders

Whether and under which conditions D-cycloserine (DCS) augments the effects of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders is unclear. To clarify whether DCS is superior to placebo in augmenting the effects of cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders and to evaluate whether antidepressants interact with DCS and the effect of potential moderating variables. PubMed, EMBASE, and PsycINFO were searched from inception to February 10, 2016. Reference lists of previous reviews and meta-analyses and reports of randomized clinical trials were also checked. Studies were eligible for inclusion if they were (1) double-blind randomized clinical trials of DCS as an augmentation strategy for exposure-based cognitive behavior therapy and (2) conducted in humans diagnosed as having specific phobia, social anxiety disorder, panic disorder with or without agoraphobia, obsessive-compulsive disorder, or posttraumatic stress disorder. Raw data were obtained from the authors and quality controlled. Data were ranked to ensure a consistent metric across studies (score range, 0-100). We used a 3-level multilevel model nesting repeated measures of outcomes within participants, who were nested within studies. Individual participant data were obtained for 21 of 22 eligible trials, representing 1047 of 1073 eligible participants. When controlling for antidepressant use, participants receiving DCS showed greater improvement from pretreatment to posttreatment (mean difference, -3.62; 95% CI, -0.81 to -6.43; P = .01; d = -0.25) but not from pretreatment to midtreatment (mean difference, -1.66; 95% CI, -4.92 to 1.60; P = .32; d = -0.14) or from pretreatment to follow-up (mean difference, -2.98, 95% CI, -5.99 to 0.03; P = .05; d = -0.19). Additional analyses showed that participants assigned to DCS were associated with lower symptom severity than those assigned to placebo at posttreatment and at follow-up. Antidepressants did not moderate the effects of DCS. None of the prespecified patient-level or study-level moderators was associated with outcomes. D-cycloserine is associated with a small augmentation effect on exposure-based therapy. This effect is not moderated by the concurrent use of antidepressants. Further research is needed to identify patient and/or therapy characteristics associated with DCS response.

Use of atypical antipsychotics and risks of cataract development in patients with schizophrenia: A population-based, nested case-control study

ObjectivePrevious research has suggested a link between typical antipsychotic use and the development of cataracts, but the association between atypical antipsychotics and cataracts remains unclear in schizophrenia (SZ). MethodsA retrospective nested case-control study was conducted using data from the National Health Insurance Database of Taiwan between the year of 2000 and 2011. A total of 2144 SZ patients with cataracts and 2222 controls matched for age, sex, and index date were included. Antipsychotic exposure was categorized by type and duration, and the association between antipsychotic exposure and cataract development was assessed using a conditional logistic regression analysis. ResultsWe found that the severity of physical comorbidities, concurrent antidepressant use, and comorbidity with glaucoma or other retinal disorders were associated with an increased risk for cataract development. Alternatively, we did not find significant associations between continuous use of clozapine, risperidone, paliperidone, ziprasidone, olanzapine, quetiapine, amisulpride, zotepine or aripiprazole and risk of cataract development in SZ patients. ConclusionsWe did not detect any association between atypical antipsychotic use and risk of cataract development in SZ patients. Future studies with longitudinal ocular evaluations in patients using atypical antipsychotics are warranted to confirm our findings.

Bipolar Disorders and Carbamazepine: Pharmacokinetics, Pharmacodynamics, Therapeutic Effects and Indications of Carbamazepine: Review of Articles

Carbamazepine is a mood stabilizer which is approved for use in bipolar disorder with manic and mixed episodes. It is also approved for use for the treatment of trigeminal neuralgia, temporal lobe epilepsy (complex partial seizures) and generalized tonic-clonic seizure. It is metabolized in the liver, primarily by CYP450 3A4 and is an inducer of CYP450 3A4 enzyme. The specific mechanism of action of carbamazepine in stabilizing mood is unknown. It exerts effects by decreasing dopamine turn over, enhancement of brain γ-aminobutyric acid (GABA) levels via multiple actions of synthesis and degradation, and modulation of other neurotransmitters, voltage sensitive Na+ channels, extra hypothalamic neuropeptides, secondary messenger systems, and neuro protection. The most common side effects are nausea, vomiting, constipation, diarrhea, loss of appetite, sedation, dizziness and ataxia. Serious side effects may include skin rashes, decreased bone marrow function and confusion. It should not be used in those with a history of bone marrow problems. Routine blood level monitoring is necessary. There is an increased risk of fetal abnormalities if carbamaepine taken in pregnancy. Carbamaepine concentrations are known to be increased with concurrent use of antidepressants (such as fluexetine, fluovoxamine, nefazodone), omeperazole, efavirnaz, ratinovir, valproate, cemitidine and erythrpmycin. Its level decrease when administrated with Rifampin and Cisplatin.

Ultra-Low-Dose Buprenorphine as a Time-Limited Treatment for Severe Suicidal Ideation: A Randomized Controlled Trial.

Suicidal ideation and behavior currently have no quick-acting pharmacological treatments that are suitable for independent outpatient use. Suicidality is linked to mental pain, which is modulated by the separation distress system through endogenous opioids. The authors tested the efficacy and safety of very low dosages of sublingual buprenorphine as a time-limited treatment for severe suicidal ideation. This was a multisite randomized double-blind placebo-controlled trial of ultra-low-dose sublingual buprenorphine as an adjunctive treatment. Severely suicidal patients without substance abuse were randomly assigned to receive either buprenorphine or placebo (in a 2:1 ratio), in addition to their ongoing individual treatments. The primary outcome measure was change in suicidal ideation, as assessed by the Beck Suicide Ideation Scale at the end of each of 4 weeks of treatment. Patients who received ultra-low-dose buprenorphine (initial dosage, 0.1 mg once or twice daily; mean final dosage=0.44 mg/day; N=40) had a greater reduction in Beck Suicide Ideation Scale scores than patients who received placebo (N=22), both after 2 weeks (mean difference -4.3, 95% CI=-8.5, -0.2) and after 4 weeks (mean difference=-7.1, 95% CI=-12.0, -2.3). Concurrent use of antidepressants and a diagnosis of borderline personality disorder did not affect the response to buprenorphine. No withdrawal symptoms were reported after treatment discontinuation at the end of the trial. The time-limited, short-term use of very low dosages of sublingual buprenorphine was associated with decreased suicidal ideation in severely suicidal patients without substance abuse. Further research is needed to establish the efficacy, safety, dosing, and appropriate patient populations for this experimental treatment.

Use of antidepressants in diabetes patients not using drugs, but only monitoring blood glucose

Objective: Patients with diabetes have an increased Odds Ratio （OR） for depressive disor- der. We wanted to investigate if patients with metabolic syndrome and/or diabetes type 2 not treated with antidiabetic agents, have an OR for concurrent antidepressant use comparable to other types of diabetes. Methods: Drug delivery data from 25 pharmacies were analysed with respect to sale of antidepressants, oral antidiabetic agents, insulin and blood glucose test strips. Results: Total population of the area was 337,019, whereas 254,083 were 18 or older. Of these 20,139 were patients receiving insulin, oral antidiabetics, glucose test strips and/or antidepressants. Those receiving antidepressants were 5.8% of those 18 or older whereas 2.4% received any antidiabetic medication (including test strips for HBGM). For patients receiving no medications but test strips alone, the adjusted OR for use concurrent use of antidepressants was 1.62 (95% confidence interval: 1.19 - 2.23), p = 0.002. For insulin-only receiving patients, the adjusted OR was 1.65 (1.41 - 1.93), p = 0.000, whereas for patients receiving only oral antidiabetics, it was 1.53 (1.38 - 1.71), p = 0.000. Patients receiving both insulin and oral antidiabetics: 2.23 (1.75 - 2.85), p = 0.000. Conclusion: Patients receiving only blood glucose strips have an OR of concurrently receiving antidepressants, not different from those receiving insulin only or oral antidiabetics only.

Chronic pain and comorbid depression

For patients with chronic pain, the experience of pain is intimately linked with psychologic distress. Epidemiologic studies indicate that depression is a common comorbidity accompanying chronic pain states. Longitudinal studies also suggest that depression can predict the emergence of chronic pain in selected populations. Emerging evidence suggests numerous pathophysiologic mechanisms that underlie the coexistence of depression and chronic pain states. Comorbid depression can complicate the presentation, clinical course, and response to treatment of patients with chronic pain. The literature reviewed herein focuses on treatment approaches applicable to chronic, nonmalignant pain states predominantly. Although antidepressants offer advantages in simultaneously producing pain relief and mitigating depression, not all antidepressants share equal efficacy; those with noradrenergic and serotonergic influences seem to fare better than agents with single neurotransmitter influences. Treatment of depression may be essential to fully enlist the patient with chronic pain in comprehensive pain management and rehabilitative approaches. Management plans of patients with chronic pain can be designed with specific individual patient needs in mind, and may involve concurrent use of antidepressants, analgesics, and psychotherapeutic approaches.

Trends in the Rate and Type of Antipsychotic Medications Prescribed to Persons With Schizophrenia

This article examines trends in antipsychotic medication use in a treated population of publicly funded patients with schizophrenia between 1991 and 1996. Findings from administrative claims data show that antipsychotic prescription rates increased from 79 percent to 83 percent between 1991 and 1996. Atypical antipsychotics were used by 39 percent of the population and comprised 41 percent of all antipsychotic agents prescribed compared to 59 percent for typical agents. Duration on a typical agent was 8 months versus 7.4 months for newer atypicals, with duration 11 months for those on clozapine. The highest switching behavior is found in users of atypicals (58% versus 25% for those on typicals) as is the percent of those who received an antidepressant concurrently with an antipsychotic, which was 44 percent for newer atypical users versus 31 percent for typical users. The lowest antidepressant use was among clozapine users (28%). Atypical users were more likely to be younger Caucasian men with higher use of inpatient and ambulatory mental health services compared to those on typical medications. The newer antipsychotic medications appear to be displacing traditional medications; however, contrary to what the literature suggests, duration is shorter and switching behavior and concurrent use of antidepressants is higher than in typical users.

Investigating the relationship between beta-blocker and antidepressant use through linkage of the administrative databases of Saskatchewan Health.

The main objectives of this research were to confirm previous reports of an increased risk of antidepressant use subsequent to propranolol therapy, and to determine whether this higher relative risk (RR) is indicative of depressive symptoms as a side-effect of the drug's use. 'New' users of beta-blockers, other antihypertensives or diuretics in two separate years were identified from records of Saskatchewan Health. Incidence of concurrent antidepressants prescribing was determined in the year after initiating therapy with a cohort drug. Medical claims were examined to identify physician services and diagnoses associated with cohort drug and antidepressant prescriptions. Risk of concurrent antidepressant use in new propanolol users aged 20-39 years was approximately double that of new diuretic users [RR 2.2 (1.5-3.3) in 1984 and 2.0 (1.1-3.5) in 1990/91]. When cases with a diagnosis of migraine headache were excluded, the risk of concurrent propranolol/antidepressant use was age- and sex-dependent, but not consistent for the two study years. It was concluded that although the risk of concurrent antidepressant use was greater in younger propranolol users, the risk cannot be solely attributed to depressive side-effects of the drug. The purposes of this paper were to present the methods employed in linking the databases of Saskatchewan Health, describe the results of the analysis, and to highlight the methodologic problems that arose.