Antidepressants in the treatment of fibromyalgia

Fibromyalgia syndrome is a chronic disease of widespread and debilitating pain whose cause is unknown and whose risk factors are poorly understood. It is often comorbid with rheumatoid and other pain disorders as well as psychiatric disorders such as anxiety and depression. Although they are not officially approved for this indication, antiepileptics and antidepressants are often used to treat fibromyalgia. The tricyclic antidepressants (TCAs), particularly amitriptyline, are among the most common treatment strategies. Because of the poor tolerability of the tricyclics, the newer antidepressants have been widely tested in fibromyalgia. The selective serotonin reuptake inhibitors (SSRIs) and the reversible monoamine oxidase inhibitors do not seem to be particularly helpful. The serotonin and norepinephrine reuptake inhibitors (SNRIs), duloxetine and milnacipran, on the other hand, have been shown in placebo-controlled trials to offer significant relief to patients suffering from fibromyalgia. Although no direct comparative studies have been performed, these compounds appear to be as effective as the TCAs but much better tolerated. The effectiveness of the SNRIs as well as other dual acting antidepressants, such as mirtazapine, but not the SSRIs, implies that a dysfunction of both serotonin and norepinephrine neurotransmission probably exists in fibromyalgia. The effectiveness of antidepressants appears to be independent of their effect on comorbid depression.     

Exacerbation of cataplexy following gradual withdrawal of antidepressants: manifestation of probable protracted rebound cataplexy

BackgroundA double-blind, placebo-controlled sodium oxybate trial provided a unique opportunity to compare changes in cataplexy following gradual withdrawal from antidepressants in narcolepsy patients.MethodsOf 228 enrolled patients, 71 discontinued antidepressant therapy. Data from 57 patients were available for analysis: 37 patients discontinued tricyclic antidepressants (TCAs) and 20 discontinued selective serotonin reuptake inhibitors (SSRIs). The trial included a 21-day withdrawal phase followed by 18-day washout and 14-day single-blind treatment phases. Two additional weeks were permitted for withdrawal from fluoxetine due to its long half-life. Weekly cataplexy attacks were recorded throughout the trial. No historical data on the frequency of cataplexy prior to treatment with antidepressants was available.ResultsAmong the patients who were and were not withdrawn from antidepressants treatment, the median frequency of baseline weekly cataplexy was similar (17.5 vs. 14.0, respectively). As expected, significant between-group differences emerged by the end of the washout period (52.04 vs. 15.25, respectively; p < 0.05); however, the frequency of cataplexy events became similar again by the end of the trial (16.5 vs. 17.5, respectively).ConclusionsPatients gradually withdrawn from antidepressants experienced a significant increase in cataplexy, but eventually returned to their baseline frequency, comparable to previously untreated control patients. Compared to SSRIs, discontinuation from TCAs was associated with a greater increase in cataplexy attacks.     

Psychopharmacologic treatment of children and adolescents with anxiety disorders

Over the last decade, psychopharmacologic treatments for pediatric anxiety disorders have been developed and increasingly subjected to randomized, controlled trials. The authors summarize the data concerning the use of tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), atypical anxiolytics, and benzodiazepines. The extant data suggest that SSRIs--both as monotherapy and when combined with psychotherapy--are effective in the treatment of pediatric anxiety disorders. In addition, some TCAs and SNRIs are effective. However, randomized controlled trials do not suggest efficacy for benzodiazepines or the atypical anxiolytic, buspirone, for children and adolescents with anxiety disorders.     

Salivary testosterone: associations with depression, anxiety disorders, and antidepressant use in a large cohort study

ObjectiveLow circulating levels of testosterone have been associated with major depression, but there is more limited evidence for differences in patients with anxiety disorders. The use of selective serotonin reuptake inhibitors (SSRIs) and other antidepressants is associated with sexual side effects, warranting testing for interactions with testosterone.MethodsData are from 722 male and 1380 female participants of The Netherlands Study of Depression and Anxiety (NESDA), who were recruited from the community, general practice care, and specialized mental health care. Depressive and anxiety diagnoses were assessed using the DSM-IV Composite International Diagnostic Interview. To smooth the episodic secretion, the four morning saliva samples per participant and the two evening samples were pooled before testosterone analysis.ResultsMorning median testosterone levels were 25.2 pg/ml in men and 16.2 pg/ml in women, with lower evening levels of 18.2 and 14.1 pg/ml, respectively. Significant determinants of testosterone levels were sex, age, time of the day, use of contraceptives, and smoking status. Female patients with a current (1-month) depressive disorder (effect size 0.29; P = 0.002), generalized anxiety disorder (0.25; P = 0.01), social phobia (0.30; P < 0.001), and agoraphobia without panic disorder (0.30; P = 0.02) had lower salivary testosterone levels than female controls. Higher testosterone levels were found in male and female participants using SSRIs than in non-users (effect size 0.26; P < 0.001).ConclusionSalivary testosterone levels are lower in female patients with a depressive disorder, generalized anxiety disorder, social phobia, and agoraphobia as compared to female controls. SSRIs may increase salivary testosterone in men and women.     

Translating the evidence on atypical depression into clinical practice

Subtypes of depression need to be recognized and diagnosed in order to properly treat patients who have depression but present with different symptoms from one another. Different pharmacotherapuetic strategies may work better for different subtypes. Selective serotonin reuptake inhibitors (SSRIs), selective norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and monoamine oxidase inhibitors (MAOIs) have been studied for the treatment of atypical depression. To date, MAOIs have been shown to be the most efficacious agents in treating atypical depression; however, many MAOIs nonselectively and irreversibly inhibit both MAO substrates, require tyramine-restricted diets, and may produce weight gain, cardiovascular side effects, or sexual dysfunction. A newer MAOI, the transdermal formulation of selegiline, may provide all of the efficacy of the older MAOIs in treating atypical depression without causing as great of adverse events and no diet restrictions.     

Cost-utility of a specific collaborative group intervention for patients with functional somatic syndromes

BackgroundCollaborative group intervention (CGI) in patients with functional somatic syndromes (FSS) has been shown to improve mental quality of life.ObjectiveTo analyse incremental cost-utility of CGI compared to enhanced medical care in patients with FSS.MethodsAn economic evaluation alongside a cluster-randomised controlled trial was performed. 35 general practitioners (GPs) recruited 300 FSS patients. Patients in the CGI arm were offered 10 group sessions within 3 months and 2 booster sessions 6 and 12 months after baseline. Costs were assessed via questionnaire. Quality adjusted life years (QALYs) were calculated using the SF-6D index, derived from the 36-item short-form health survey (SF-36). We calculated patients' net-monetary-benefit (NMB), estimated the treatment effect via regression, and generated cost-effectiveness acceptability curves.ResultsUsing intention-to-treat analysis, total costs during the 12-month study period were 5777EUR in the intervention, and 6858EUR in the control group. Controlling for possible confounders, we found a small, but significant positive intervention effect on QALYs (+ 0.017; p = 0.019) and an insignificant cost saving resulting from a cost-increase in the control group (− 10.5%; p = 0.278). NMB regression showed that the probability of CGI to be cost-effective was 69% for a willingness to pay (WTP) of 0EUR/QALY, increased to 92% for a WTP of 50,000EUR/QALY and reached the level of 95% at a WTP of 70,375EUR/QALY. Subgroup analyses yielded that CGI was only cost-effective in severe somatic symptom severity (PHQ-15 ≥ 15).ConclusionCGI has a high probability to be a cost-effective treatment for FSS, in particular for patients with severe somatic symptom severity.     

Treatment of depression in patients with heart disease.

There is a growing body of evidence that depression significantly and adversely affects cardiovascular health. Perhaps the most prominent finding is the documented increase in mortality rate in patients with depression after myocardial infarction. The critical questions of interest to both the clinician and researcher are whether there are safe and effective treatments for depression in patients with heart disease and whether treatment of depression reduces the increased risk of cardiac morbidity and mortality. Though the data are limited and are primarily from open or comparator trials, the tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and specific psychotherapies appear to be effective for treatment of depression in patients with ischemic heart disease (IHD), and response rates are comparable to those reported in depressed patients without heart disease; however, there has been only one placebo-controlled trial to date, and therefore it is premature to come to definitive conclusions regarding the efficacy of antidepressant therapies in this patient population. With respect to safety, the TCAs are associated with documented adverse cardiovascular effects, including increases in heart rate, orthostatic hypotension, and conduction delays. Use of TCAs in patients with IHD carries a proven increased risk of cardiac morbidity and perhaps of mortality as well. The SSRIs appear to be relatively safe and effective treatment for depression in patients with comorbid IHD.     

Differential effects of perinatal exposure to antidepressants on learning and memory,acoustic startle,anxiety, and open-field activity in Sprague-Dawley rats

Most antidepressants inhibit monoamine reuptake. Selective serotonin (5-HT) reuptake inhibitors (SSRIs) act on the 5-HT transporter (SERT) whereas norepinephrine-dopamine reuptake inhibitors (NDRIs) act on the norepinephrine and dopamine transporters. Epidemiological reports link SSRI use during pregnancy to an increased prevalence of autism spectrum disorder (ASD). We previously showed that perinatal exposure to the SSRI citalopram (CIT) results in rodent offspring that exhibit a number of behaviors consistent with an ASD-like phenotype. The present study examined the effect of perinatal exposure to CIT (at a lower dose), another SSRI, fluoxetine (FLX), and an NDRI, bupropion (BUP). Gravid Sprague-Dawley rats were subcutaneously injected twice per day (6 h apart) with 5 mg/kg CIT, 5 mg/kg FLX, 15 mg/kg BUP, or saline (SAL) from embryonic day (E) 6–21, and directly to the pups from postnatal day (P) 1–20. As adults, one male/female from each litter was given one of a series of tests. Both SSRI-exposed groups showed spatial learning deficits in Morris and radial water mazes, increased marble burying, increased acoustic startle, hypoactivity, and attenuated activity to the stimulating effect of the NMDA-R antagonist MK-801. The BUP-exposed group showed a reduction in elevated zero-maze quadrant entries and increased stimulated open-field activity following (+)-amphetamine challenge. These results reinforce concern about the use of antidepressants during pregnancy and highlight how the two classes of drugs produce different constellations of effects with more effects associated with the SSRIs. Further investigation into how antidepressants alter brain development leading to enduring adverse neurobehavioral effects is warranted.     

Pensamiento catastrófico ante el dolor: presencia en una población de migrañosos

IntroductionCatastrophic thought refers to a negative cognitive and emotional response to pain, and is thought to contribute to pain chronification. We aimed to evaluate pain catastrophising PC in a population of patients with migraine.MethodsWe collected sociodemographic data and clinical data on migraine from patients attended at a tertiary hospital headache unit between January and June 2015. PC was measured with the Spanish-language version of the Pain Catastrophizing Scale (PCS). We compared presence of PC in patients with episodic and chronic migraine, and its correlation with clinical impact (measured by the Headache Impact Test-6 [HIT-6] scale), comorbid depression and anxiety (measured with the Hospital Anxiety and Depression Scale [HADS]), and the presence of medication overuse.ResultsThe study included 96 patients (16 men and 80 women); 67 (69.8%) were diagnosed with chronic migraine and 29 (30.2%) with episodic migraine. Migraine impact was at least moderate (HIT-6 ≥ 56) in 85.4% of cases, and 24% exceeded the cut-off point for anxiety and 9.4% for depression. A total of 34.4% presented PC. Patients with chronic migraine scored higher than those with episodic symptoms on the HADS for anxiety (P < .001) and depression (P < .001) and on the HIT-6 (P < .001).ConclusionsPC is common among patients with migraine. It is related to migraine severity and to comorbid anxiety and depression. PC does not appear to increase the likelihood of migraine chronification or medication overuse.     

Treatment of depression in patients with temporal lobe epilepsy: A pilot study of cognitive behavioral therapy vs. selective serotonin reuptake inhibitors

There is a high prevalence of depression in patients with epilepsy, which negatively impacts their quality of life (QOL) and seizure control. Currently, the first-line of treatment for depression in patients with epilepsy is based on selective serotonin reuptake inhibitors (SSRIs). The main objective of this pilot study was to compare cognitive behavioral therapy (CBT) versus SSRIs for the treatment of major depressive disorder (MDD) in patients with temporal lobe epilepsy (TLE). Seven patients who received group CBT were compared with eight patients treated with SSRIs. All were diagnosed with MDD and TLE. Patients were assessed at baseline before treatment and at six and 12 weeks during treatment with the Quality of Life in Epilepsy Scale of 31 items (QOLIE 31), the Beck Depression Inventory (BDI), and the Hospital Anxiety and Depression Scale (HADS). Seizure records were also taken on a monthly basis. After 12 weeks of treatment, both groups showed improved QOL and reduced severity of depression symptoms. There were no statistically significant group differences in the final scores for the BDI (p = 0.40) and QOLIE 31 (p = 0.72), although the effect size on QOL was higher for the group receiving CBT. In conclusion, the present study suggests that both CBT and SSRIs may improve MDD and QOL in patients with TLE. We found no significant outcome differences between both treatment modalities. These findings support further study using a double-blind controlled design to demonstrate the efficacy of CBT and SSRIs in the treatment of MDD and QOL in patients with TLE.     

Utilization patterns of antidepressants between 1991 and 2011 in a population-based cohort of middle-aged and elderly

BackgroundIn middle-aged and older patients in whom antidepressant use increased in last decades, patterns of use might be of concern The objective of this study was to investigate the patterns of prevalence, incidence and duration of antidepressant use in an ageing population.MethodsAll participants (aged > 45 years) from the population-based Rotterdam Study were followed from January 1st 1991 until death, loss to follow-up, or end of the study period (December 31st 2011). Antidepressant drug dispensing, based on pharmacy records, were subdivided into Tricyclic Antidepressants (TCAs), Selective Serotonin Reuptake Inhibitors (SSRIs) and other antidepressants. One-year prevalence, 5-year incidence and duration of antidepressant use were calculated.ResultsYearly prevalence of antidepressant use increased from 3.9% in 1991 to 8.3% of the population in 2011. The increase in SSRI use was 5.8-fold, whereas use of other antidepressants doubled and TCA use remained stable over time. Incidence of all antidepressants decreased from 23.9 to 14.2 per 1000 person-years between 1992 and 2011. The duration of a first treatment episode increased over time.ConclusionDespite the prevalence of antidepressant use increased over time, incidence did not, which is most likely explained by a longer treatment duration and recurrent episodes.     

Association between number of comorbid conditions,depression, and sleep quality using the Pittsburgh Sleep Quality Index: Results from a population-based survey

ObjectivesAlthough sleep problems are a serious public concern, it is not clear if the presence of depression or multiple comorbid conditions has an additive or multiplicative effect on sleep quality.MethodsWe conducted a population-based, cross-sectional survey in a rural town in Japan. Multivariable-adjusted linear regression models were used to explore the association between the number of comorbid conditions and the Pittsburgh Sleep Quality Index (PSQI) global score. The association between the number of comorbid conditions and presence of depression, as defined by the five-item Mental Health Inventory (scores ? 60), in those with poor quality sleep (PSQI global score > 5) was determined using a non-parametric trend test.ResultsOf 5107 respondents, 3403 (mean age: 51.0 years, women: 52.6%) were used for the analysis after exclusion of missing PSQI data. The PSQI global score (mean: 4.9) increased as the number of comorbid conditions increased in a linear and statistically significant manner (p < 0.0001). The PSQI global score increased by 0.374 for each additional comorbid condition (p < 0.0001). Among those with poor sleep quality, the proportion with depression increased significantly and linearly (p < 0.0001) as the number of comorbid conditions increased (37.5% for 0 vs. 59.9% for ?4 comorbid conditions).ConclusionThe number of comorbid conditions correlated positively with poor sleep quality, and as the number of comorbid conditions increased, the proportion of those also suffering from depression increased. Recognizing the signs of depression in patients with multiple comorbid conditions is important because of its exacerbation of poor sleep quality.     

Antidepressants and suicidal behaviour in unipolar depression

OBJECTIVE: To compare the rates of suicidal behaviour during vs. after discontinuation of treatment with antidepressants, and to determine the comparative rates of suicidal behaviour for patients maintained on tricyclic (TCA) vs. selective serotonin reuptake inhibitor (SSRI) antidepressants. METHOD: Charts were reviewed for 521 patients with major depressive disorder and/or dysthymic disorder. Periods of active treatment or discontinuation with SSRIs or TCAs were determined. Rates of completed suicide, suicide attempts, and hospitalization for suicidality were analyzed. RESULTS: There was greater than a five-fold increase in risk for suicidal behaviour after discontinuation of antidepressant treatment (P < 0.0001). The rates of suicidal behavior during treatment with SSRIs or TCAs were similar. CONCLUSION: Suicidal behaviour in unipolar depressed patients treated with antidepressants increases substantially after medication discontinuation. This effect occurred in both patients who were maintained on SSRIs and TCAs. The findings support a possible protective effect on suicidal behaviour for both SSRIs and TCAs.     

SSRIs vs. TCAs in the treatment of panic disorder: a meta-analysis

OBJECTIVE: To compare the short-term efficacy of selective serotonin reuptake inhibitors (SSRIs) vs. tricyclic antidepressants (TCAs) in the treatment of panic disorder (PD) a meta-analysis was conducted. METHOD: Included were 43 studies (34 randomized, nine open), pertaining to 53 treatment conditions, 2367 patients at pretest and 1804 at post-test. Outcome was measured with the proportion of patients becoming panic-free, and with pre/post Cohen's d effect sizes, calculated for four clinical variables: panic, agoraphobia, depression, and general anxiety. RESULTS: There were no differences between SSRIs and TCAs on any of the effect sizes, indicating that both groups of antidepressants are equally effective in reducing panic symptoms, agoraphobic avoidance, depressive symptomatology and general anxiety. Also the percentage of patients free of panic attacks at post-test did not differ. The number of drop-outs, however, was significantly lower in the group of patients treated with SSRIs (18%) vs. TCAs (31%). CONCLUSION: SSRIs and TCAs are equal in efficacy in the treatment of panic disorder, but SSRIs are tolerated better.     

Depression in patients with Parkinson's disease.

Parkinson's disease (PD) is a disabling neurodegenerative condition commonly complicated by the existence of comorbid depression. The prevalence rates of depression in this patient group have been reported to be as high as 40%. Currently, depression in PD is undertreated; there have been few controlled clinical trials of antidepressants in this patient group. Patients with PD are usually elderly and often administered a range of medication, therefore the choice of antidepressant must be undertaken with care. Tricyclic antidepressants (TCAs) have been studied in patients with PD and comorbid depression; however, the risk of anticholinergic side-effects means that their use is largely avoided. Selective serotonin reuptake inhibitors have comparable efficacy to the TCAs and a better tolerability profile in patients with depression; they are rapidly being considered as first-line therapy for PD patients with depression. Clinical studies in this patient group are warranted. This article reviews the characteristics of comorbid depression in patients with PD and discusses the treatment options available.     

Antidepressant prescribing in nursing homes: is there a place for tricyclics?

OBJECTIVE: To deduce a model describing physicians' choice of antidepressants for treating elderly nursing home patients. METHODS: Subjects were geriatric residents of 137 skilled nursing facilities who regularly received an antidepressant medication for at least one month (n = 3,440, 28% of all residents). Reasons for prescribing antidepressants and physicians' diagnoses of depression and dementia were identified by medical record audit. Residents were grouped by dementia and antidepressant target symptoms (depression, or one or more non-psychiatric symptoms, i.e. insomnia, pain, incontinence, itching). RESULTS: Selective serotonin reuptake inhibitors (SSRIs) were prescribed preferentially over tricyclic antidepressants (TCAs) for treating depression in both demented and non-demented residents, but TCAs were nine times more likely to be prescribed for treating non-psychiatric target symptoms alone. When non-psychiatric target symptoms were present without depression or dementia, both amitriptyline and nortriptyline prescribing was increased, but amitriptyline appeared to be the antidepressant of choice. In all subgroups examined, its use was two to five times more prevalent when such symptoms were present. In patients with dementia, amitriptyline prescribing declined whether or not non-psychiatric target symptoms were present, but nortriptyline prescribing did not; nortriptyline was three times more likely than amitriptyline to be prescribed in the presence of dementia. CONCLUSIONS: Physicians prescribe anticholinergic TCAs principally to treat common non-depressive symptoms in nursing home residents, preferring SSRIs for uncomplicated depression and depression with dementia. They tend to avoid prescribing anticholinergic TCAs other than nortriptyline when they recognize a patient as demented. The data suggest that physicians employ a decision model for antidepressant prescribing that simultaneously recognizes the utility of TCAs in treating non-psychiatric symptoms and the anticholinergic vulnerability of older, especially demented, patients. Whether or not this model leads to optimal patient management requires further study.     

Enhancing central noradrenergic function in depression: is there still a place for a new antidepressant?

Noradrenaline has long played a key role in the way the etiology of depression is conceptualized and in the mechanism of action of many current antidepressants. Tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), serotonin-noradrenaline reuptake inhibitors (SNRIs), selective noradrenaline reuptake inhibitors (NRIs), the noradrenergic and specific serotonergic antidepressant (NaSSA) mirtazapine, and many atypicals, like mianserin and bupropion, influence, at least in part, central noradrenergic function. Enhancement of noradrenergic function may be particularly helpful in patients with melancholia. However, while noradrenaline will continue to be a target for research into the etiology and treatment of depression, it is unlikely that antidepressants acting solely on noradrenaline will be pursued.     

When ageing meets the blues: Are current antidepressants effective in depressed aged patients?

“I had to wait 110 years to become famous. I wanted to enjoy it as long as possible.”, Jeanne Louise Calment (1875–1997).This review summarizes current knowledge of the effects of antidepressant drugs in elderly patients (double-blind placebo (n = 27) or active comparator-controlled clinical trials (n = 21) indexed in Pubmed in depressed patients aged ≥60) and in aged mice (≥9 months) and middle-aged rats (≥14 months) on depression-related symptoms and cognitive performances. Finally, other potential therapeutic targets for treating depression-related disorders in elderly patients are also addressed (neurogenesis, GABA_B receptor, 5-HT₄ receptor, mTOR signaling). Overall, the very few published preclinical studies (n = 12 in total) in middle-aged and aged rodents seem to suggest that selective serotonin reuptake inhibitors (SSRIs) may be less effective than tricyclic antidepressant drugs (TCAs) in ameliorating depression-like behavior and cognitive functions. On the other hand, results from clinical trials suggest that there is not a marked difference in efficacy and safety profiles of current marketed classes of antidepressant drugs.