Switching, Induction of Rapid Cycling, and Increased Suicidality With Antidepressants in Bipolar Patients: Fact or Overinterpretation?

CNS Spectrums ◽  
2008 ◽  
Vol 13 (9) ◽  
pp. 790-795 ◽  
Author(s):  
Heinz C.R. Grunze

AbstractAntidepressants constitute a central cornerstone in the treatment of depressive syndromes. In bipolar patients, however, there is an ongoing controversy about their usefulness for at least 3 decades. Early reports, mainly concerning tricyclic antidepressants, have repeatedly pointed toward unfavorable side effects on the course of the disorder, namely switching into (hypo)mania, induction of rapid cycling, and increased risk of suicide. Most evidence for both unfavorable and favorable effects has been deducted, thus far, from small studies with methodological flaws. More substantiated evidence only recently became available. From this it appears that, at least, the switch risk, and perhaps also the risk for rapid cycling and new-onset suicidality have been overinterpreted. At the same time, these new data raise doubt about the efficacy of anti-depressants as a primary-treatment choice in bipolar depression.

2006 ◽  
Vol 189 (2) ◽  
pp. 124-131 ◽  
Author(s):  
R. M. Post ◽  
L. L. Altshuler ◽  
G. S. Leverich ◽  
M. A. Frye ◽  
W A. Nolen ◽  
...  

BackgroundFew studies have examined the relative risks of switching into hypomania or mania associated with second-generation antidepressant drugs in bipolar depression.AimsTo examine the relative acute effects of bupropion, sertraline and venlafaxine as adjuncts to mood stabilisers.MethodIn a 10-week trial, participants receiving out-patient treatment for bipolar disorder (stratified for rapid cycling) were randomly treated with a flexible dose of one of the antidepressants, or their respective matching placebos, as adjuncts to mood stabilisers.ResultsA total of 174 adults with bipolar disorder I, II or not otherwise specified, currently in the depressed phase, were included. All three antidepressants were associated with a similar range of acute response (49–53%) and remission (34–41%). There was a significantly increased risk of switches into hypomania or mania in participants treated with venlafaxine compared with bupropion or sertraline.ConclusionsMore caution appears indicated in the use of venlafaxine rather than bupropion or sertraline in the adjunctive treatment of bipolar depression, especially if there is a prior history of rapid cycling.


2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Kyle J. Burghardt ◽  
Kristen N. Gardner ◽  
Joshua W. Johnson ◽  
Vicki L. Ellingrod

Atypical antipsychotics have become a common therapeutic option in both schizophrenia and bipolar disorder. However, these medications come with a high risk of metabolic side effects, particularly dyslipidemia and insulin resistance. Therefore, identification of patients who are at increased risk for metabolic side effects is of great importance. The genetics of fatty acid metabolism is one area of research that may help identify such patients. Therefore, in this present study, we aimed to determine the effect of one commonly studied genetic polymorphism from both fatty acid desaturase 1 (FADS1) and FADS2 gene on a surrogate measure of insulin resistance and lipid levels in a metabolically high-risk population of patients largely exposed to atypical antipsychotics. This study used a cross-sectional design, fasting blood draws, and genetic analysis to investigate associations between polymorphisms, haplotypes, and metabolic measures. A total of 320 subjects with schizophrenia (n=226) or bipolar disorder (n=94) were included in this study. The mean age of the population was 42.5 years and 45% were male. A significant association between FADS1 and FADS2 haplotypes was found with insulin resistance while controlling for confounders. Further investigation is required to replicate this finding.


2013 ◽  
Vol 28 (S2) ◽  
pp. 97-98
Author(s):  
C. Brichant-Petitjean

The treatment of bipolar depression is still an important challenge for clinicians and the number of evidence based options is limited. Antidepressants are the most frequently prescribed drugs for bipolar depression in clinical practice, even though the relative risks and benefits of using this treatment strategy has been strongly debated over the past 25 years. One of the reasons is that several placebo-controlled studies have shown that antidepressants could induce manic or hypomanic episodes and accelerate the rate of cycling, worsening the course of the illness by increasing the number of mood episodes over time. Antidepressant-Induced Manias (AIM) have been reported in a subgroup of about 25 to 30% of bipolar patients. There is an increased risk of mood switch with tricyclic antidepressants (TCAs) and serotonin and noradrenaline reuptake inhibitors (SNRIs). The occurrence of mania during antidepressant treatment is a crucial issue in the clinical management of Bipolar Disorder (BD) since it greatly interferes with the establishment of an optimal treatment for bipolar depression. It can have substantial negative impact on overall mood and psychosocial stability in patients receiving treatment for bipolar depression, possibly leading to treatment resistance. Therefore, the identification of clinical correlates associated with AIM is essential to better identify at-risk subgroups of patients and propose specific individualized treatment strategies for bipolar depression. No risk factors has been replicated so far, mostly because studies are characterized by small sample sizes and by the absence of a consensus definition of AIM, showing conflicting results. In this study, patients were classified according to a restrictive definition, similar to that used by Rousseva et al. (2003). An AIM− group (n = 135) was compared to AIM+ patients (n = 75) for clinical and sociodemographic factors as well as for psychological dimensions.


2007 ◽  
Vol 30 (4) ◽  
pp. 95
Author(s):  
Valerie Taylor ◽  
Glenda M. MacQueen

Bipolar disorder and major depression are life-shortening illnesses. Unnatural causes such as suicide and accidents account for only a portion of this premature mortality1 Research is beginning to identify that mood disordered patients have a higher incidence of metabolic syndrome, an illness characterized by dyslipidemia, impaired glucose tolerance, hypertension and obesity.2 Metabolic syndrome is associated with an increased risk for a variety of physical illnesses. Hypothesis: Never treated patients with mood disorders have preexisting elevations in the prevalence of the component variables of metabolic syndrome. Central obesity will be especially elevated, predicting increased premature mortality. Methods: We assessed never treated patients with mood disorders for metabolic syndrome and its component variables. Patients were assessed at baseline and followed up at 6-month intervals. All psychiatric pharmacotherapy was documented. Body mass index (BMI) was also obtained and the percentage of deaths attributable to overweight and obesity was calculated using the population attributable risk (PAR). [PAR= ∑[P (RR-1)/RR] Results: Prior to the initiation of treatment, patients did not differ from population norms with respect to metabolic syndrome or BMI. At 2-year follow-up, BMI had increased for unipolar patients 2.02 points and 1.92 points for bipolar patients. (p < .001) This increase in BMI predicted an increase in mortality of 19.4%. Conclusion: An increase in visceral obesity is often the first component of metabolic syndrome to appear and may indicate the initiation of this disease process prematurely in this group. The increase in BMI places patients with mood disorders at risk for premature mortality and indicates a need for early intervention. References 1.Osby U, Brandt L, Correia N, Ekbom A & Sparen P. Excess mortability in bipolar and Unipolar disorder rin Sweden. Archives of General Psychiatry, 2001;58: 844-850 2.Toalson P, Saeeduddin A, Hardy T & Kabinoff G. The metabolic syndrome in patients with severe mental illness. Journal of Clinical Psychiatry, 2004; 6(4): 152-158


2021 ◽  
Vol 10 (13) ◽  
pp. 2927
Author(s):  
Amaar Obaid Hassan ◽  
Gregory Y. H. Lip ◽  
Arnaud Bisson ◽  
Julien Herbert ◽  
Alexandre Bodin ◽  
...  

There are limited data on the relationship of acute dental infections with hospitalisation and new-onset atrial fibrillation (AF). This study aimed to assess the relationship between acute periapical abscess and incident AF. This was a retrospective cohort study from a French national database of patients hospitalized in 2013 (3.4 million patients) with at least five years of follow up. In total, 3,056,291 adults (55.1% female) required hospital admission in French hospitals in 2013 while not having a history of AF. Of 4693 patients classified as having dental periapical abscess, 435 (9.27%) developed AF, compared to 326,241 (10.69%) without dental periapical abscess that developed AF over a mean follow-up of 4.8 ± 1.7 years. Multivariable analysis indicated that dental periapical abscess acted as an independent predictor for new onset AF (p < 0.01). The CHA2DS2VASc score in patients with acute dental periapical abscess had moderate predictive value for development of AF, with Area Under the Curve (AUC) 0.73 (95% CI, 0.71–0.76). An increased risk of new onset AF was identified for individuals hospitalized with dental periapical abscess. Careful follow up of patients with severe, acute dental periapical infections is needed for incident AF, as well as investigations of possible mechanisms linking these conditions.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
B Zareini ◽  
P.B Blanche ◽  
A.H Holt ◽  
M.M Malik ◽  
D.P Rajan ◽  
...  

Abstract Background Development of type 2 diabetes (T2D) is common in patients with heart failure (HF), but knowledge of future cardiovascular events is lacking. Purpose We compared risk of heart failure hospitalization (HFH) or death versus ischemic events in real-life HF patients with new-onset T2D, prevalent T2D and no T2D. Methods Using the Danish nationwide registers, we identified all patients with HF between 1998–2016. The patients were separated in two different HF cohorts based on the status of T2D. One cohort consisted of HF patients with either prevalent or absent T2D at the time of HF diagnosis. The other cohort consisted of HF patients, who developed new-onset T2D, included at time of diagnosis. The two HF cohorts were analyzed separately. Outcomes for both cohorts were analyzed as time-to-first event as either an ischemic event (i.e. composite outcome of fatal and non-fatal myocardial infarction, stroke, and peripheral artery disease), HFH, or event-free death (not related to HFH or the ischemic event). For each cohort, we estimated the five-year absolute risk of ischemic event, HFH and event-free death, along with five-year risk ratio of HFH or event-free death versus ischemic events. Effects among subgroups were investigated by stratifying both cohorts based on age, gender and comorbidities present at inclusion. Results A total of 139,264 HF patients were included between 1998 and 2016, of which 29,078 (21%) patients had prevalent T2D at baseline. A total of 11,819 (8%) developed new-onset T2D and were included in the second cohort. The median duration of time between HF diagnosis and new-onset T2D diagnosis was: 4.1 years (IQR:1.5; 5.8). The absolute five-year risk of an ischemic event in patients with new-onset T2D, prevalent T2D and no T2D was: 17.9% (95% confidence interval (CI): 17.2; 18.6), 26.1% (95% CI: 25.6; 26.7), and 18.8% (95% CI:18.6; 19.0). Corresponding estimates for HFH were: 31.5% (95% CI: 30.6; 32.3), 33.6% (95% CI: 33.0; 34.2), and 30,7% (95% CI: 30.5; 31.0). The absolute five-year risk of event-free death among patients with new-onset T2D, prevalent T2D and no T2D was: 20.9% (95% CI: 20.2; 21.7), 18.9% (95% CI:18.4; 19.3), and 18.6% (95% CI: 18.4; 18.8) (see Figure). The five-year risk ratio of experiencing HFH or event-free death versus an ischemic event was: 2.9 (95% CI: 2.8; 3.1), 2.0 (95% CI:2.0; 2.1), and 2.6 (95% CI: 2.6; 2.7) for patients with new-onset T2D, prevalent T2D and no T2D, respectively. Similar results of absolute and relative risk were present across all subgroups. Conclusion In our population of HF patients, 8% developed new-onset diabetes. Development of T2D in patients with HF increases the risk of HFH and mortality three-fold. The increased risk of new-onset T2D is higher than the importance of prevalent T2D in patients with HF. Funding Acknowledgement Type of funding source: None


Author(s):  
Ranjit Unnikrishnan ◽  
Anoop Misra

AbstractThe advent and rapid spread of the coronavirus disease-2019 (COVID19) pandemic across the world has focused attention on the relationship of commonly occurring comorbidities such as diabetes on the course and outcomes of this infection. While diabetes does not seem to be associated with an increased risk of COVID19 infection per se, it has been clearly demonstrated that the presence of hyperglycemia of any degree predisposes to worse outcomes, such as more severe respiratory involvement, ICU admissions, need for mechanical ventilation and mortality. Further, COVID19 infection has been associated with the development of new-onset hyperglycemia and diabetes, and worsening of glycemic control in pre-existing diabetes, due to direct pancreatic damage by the virus, body’s stress response to infection (including cytokine storm) and use of diabetogenic drugs such as corticosteroids in the treatment of severe COVID19. In addition, public health measures taken to flatten the pandemic curve (such as lockdowns) can also adversely impact persons with diabetes by limiting their access to clinical care, healthy diet, and opportunities to exercise. Most antidiabetic medications can continue to be used in patients with mild COVID19 but switching over to insulin is preferred in severe disease.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ranjit Unnikrishnan ◽  
Anoop Misra

AbstractThe advent and rapid spread of the coronavirus disease-2019 (COVID19) pandemic across the world has focused attention on the relationship of commonly occurring comorbidities such as diabetes on the course and outcomes of this infection. While diabetes does not seem to be associated with an increased risk of COVID19 infection per se, it has been clearly demonstrated that the presence of hyperglycemia of any degree predisposes to worse outcomes, such as more severe respiratory involvement, ICU admissions, need for mechanical ventilation and mortality. Further, COVID19 infection has been associated with the development of new-onset hyperglycemia and diabetes, and worsening of glycemic control in pre-existing diabetes, due to direct pancreatic damage by the virus, body’s stress response to infection (including cytokine storm) and use of diabetogenic drugs such as corticosteroids in the treatment of severe COVID19. In addition, public health measures taken to flatten the pandemic curve (such as lockdowns) can also adversely impact persons with diabetes by limiting their access to clinical care, healthy diet, and opportunities to exercise. Most antidiabetic medications can continue to be used in patients with mild COVID19 but switching over to insulin is preferred in severe disease.


2020 ◽  
pp. bjophthalmol-2020-316293
Author(s):  
Puneet Jain ◽  
Paul T Finger ◽  
Maria Fili ◽  
Bertil Damato ◽  
Sarah E Coupland ◽  
...  

BackgroundTo relate conjunctival melanoma characteristics to local control.MethodsRetrospective, registry-based interventional study with data gathered from 10 ophthalmic oncology centres from 9 countries on 4 continents. Conjunctival melanoma patients diagnosed between January 2001 and December 2013 were enrolled in the study. Primary treatments included local excision, excision with cryotherapy and exenteration. Adjuvant treatments included topical chemotherapy, brachytherapy, proton and external beam radiotherapy (EBRT). Cumulative 5-year and 10-year Kaplan-Meier local recurrence rates were related to clinical and pathological T-categories of the eighth edition of the American Joint Committee on Cancer (AJCC) staging system.Results288 patients had a mean initial age of 59.7±16.8 years. Clinical T-categories (cT) were cT1 (n=218,75.7%), cT2 (n=34, 11.8%), cT3 (n=15, 5.2%), cTx (n=21,7.3%) with no cT4. Primary treatment included local excision (n=161/288, 55.9%) followed by excision biopsy with cryotherapy (n=108/288, 37.5%) and exenteration (n=5/288, 1.7%). Adjuvant therapies included topical mitomycin (n=107/288, 37.1%), plaque-brachytherapy (n=55/288, 19.1%), proton-beam (n=36/288, 13.5%), topical interferon (n=20/288, 6.9%) and EBRT (n=15/288, 5.2%). Secondary exenteration was performed (n=11/283, 3.9%). Local recurrence was noted in 19.1% (median=3.6 years). Cumulative local recurrence was 5.4% (3.2–8.9%), 19.3% (14.4–25.5%) and 36.9% (26.5–49.9%) at 1, 5 and 10 years, respectively. cT3 and cT2 tumors were twice as likely to recur than cT1 tumours, but only cT3 had statistically significantly greater risk of local recurrence than T1 (p=0.013). Factors such as tumour ulceration, plica or caruncle involvement and tumour thickness were not significantly associated with an increased risk of local recurrence.ConclusionThis multicentre international study showed that eighth edition of AJCC tumour staging was related to the risk of local recurrence of conjunctival melanoma after treatment. The 10-year cumulative local recurrence remains high despite current management.


Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 630 ◽  
Author(s):  
Annalisa Noce ◽  
Manuela Di Lauro ◽  
Francesca Di Daniele ◽  
Anna Pietroboni Zaitseva ◽  
Giulia Marrone ◽  
...  

Metabolic syndrome (MetS) is a clinical manifestation characterized by a plethora of comorbidities, including hyperglycemia, abdominal obesity, arterial hypertension, and dyslipidemia. All MetS comorbidities participate to induce a low-grade inflammation state and oxidative stress, typical of this syndrome. MetS is related to an increased risk of cardiovascular diseases and early death, with an important impact on health-care costs. For its clinic management a poly-pharmaceutical therapy is often required, but this can cause side effects and reduce the patient’s compliance. For this reason, finding a valid and alternative therapeutic strategy, natural and free of side effects, could represent a useful tool in the fight the MetS. In this context, the use of functional foods, and the assumption of natural bioactive compounds (NBCs), could exert beneficial effects on body weight, blood pressure and glucose metabolism control, on endothelial damage, on the improvement of lipid profile, on the inflammatory state, and on oxidative stress. This review focuses on the possible beneficial role of NBCs in the prevention and in the clinical management of MetS and its comorbidities.


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