Depression and pain: An appraisal of cost effectiveness and cost utility of antidepressants

BackgroundAlthough depression and chronic pain frequently co-occur, there is a lack of clarity in the literature regarding the cost-effectiveness and cost-utility of antidepressants in the presence of these two conditions. From the perspective of healthcare provider, the current study aims to compare the cost-effectiveness and cost-utility of antidepressants in a national cohort of depressed patients with and without comorbid pain conditions.MethodsAdult patients prescribed with antidepressants for depression were identified from the National Health Insurance Research Database in Taiwan (n = 96,501). By using remission as effectiveness measure and quality-adjusted life years (QALYs) as utility measure, the cost-effectiveness and cost-utility were compared across selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), and tricyclic antidepressants (TCAs), as well as by the presence of comorbid painful physical symptoms (PPS).ResultsSSRIs dominated SNRIs in both the cost-effectiveness and cost-utility regardless of comorbid PPS. In comparison with TCAs, SSRIs were likely to be the cost-effective option for patients without PPS. In patients with PPS, the cost-utility advantage for SSRIs over TCAs varied with threshold willingness-to-pay levels. Comorbid PPS may be considered an effect modifier of the cost-utility comparisons between SSRIs and TCAs.ConclusionsFor depressed patients without PPS, SSRIs are likely to be cost-effective in improving remission rates and QALYs compared to TCAs and SNRIs. However, to improve cost-utility in those with comorbid PPS, people need to choose between SSRIs and TCAs according to threshold willingness-to-pay levels. Future research is warranted to clarify the impacts of different pain conditions on the economic evaluations of pharmacological treatments in patients with depression.     

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.     

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.     

The place for the tricyclic antidepressants in the treatment of depression.

OBJECTIVE: The new generation antidepressants have been an important advance in the treatment of depression. Since their introduction, their use has become widespread and the role of the older tricyclic antidepressants (TCAs) has been suggested only as a second-line choice. This assumption is questioned and the role of the TCAs as a first-line treatment for severe depression is discussed. METHOD: The relevant literature concerning the efficacy, tolerability and safety of the antidepressant drugs is reviewed, particularly those studies which compare the newer antidepressant agents with the TCAs. RESULTS: The newer agents are equally as efficient as the tricyclics in the treatment of mild to moderate depression. There are indications that the TCAs are more efficacious for severe depression. The tolerability of the drugs appear about equivalent in terms of discontinuation rates; however, the side effects are different and clinicians need to be mindful of drug interactions and the potential of the serotonin syndrome with the selective serotonin re-uptake inhibitors (SSRIs), problems not found with the TCAs. The TCAs are potentially lethal in overdose; however, appropriate clinical management appears to be a more important issue than the toxicity of the medication. CONCLUSIONS: The newer antidepressant agents are important advances in the treatment of depression. However, the TCAs still have an important place as the first-line treatment for patients with severe (melancholic/endogenous) depression.     

Antidepressants in the treatment of psychosis with comorbid depression in Parkinson disease

Psychotic symptoms are commonly associated with Parkinson disease and can be a source of significant morbidity. Depression has been reported as a comorbidity in patients with psychosis. We describe a patient with Parkinson disease with psychotic symptoms and comorbid depression whose treatment refractory delusions and hallucinations improved markedly only after antidepressant monotherapy was initiated. The phenomenology of the delusions was atypical for those found in Parkinson or in depression. Psychotic symptoms refractory or only partially responsive to conventional treatment should prompt a search for potential underlying psychiatric comorbidities. Given case reports of exacerbation of psychotic symptoms with antidepressants, we emphasize careful identification and active follow up of the comorbid depressive disorders in PD patients with psychosis. Potential mechanisms implicated in the response of psychosis to antidepressants are discussed.     

The use of antidepressants for headache prophylaxis

The focus of this review is on the efficacy of antidepressants as preventive treatments for migraine and chronic tension-type headache (TTH). Pharmacologic prophylaxis may be indicated for patients with frequent headaches, who respond insufficiently to acute therapies, or for whom medication overuse is a concern. The well-documented efficacy of the tricyclic antidepressant amitriptyline, both for migraine and chronic TTH, has been followed by widespread use of other antidepressants for headache prophylaxis. Although antidepressants in general share comparable efficacy for the treatment of depressive disorders, their efficacy as headache preventives varies widely. Evidence supporting use of the selective serotonin reuptake inhibitors as headache preventives is poor; their use should be reserved for treating comorbid depression in a patient who also has a headache disorder. Small randomized trials of venlafaxine indicate preliminary efficacy both for migraine and tension-type headache. Evidence for other antidepressants is lacking. Although antidepressants are often prescribed to headache patients under the assumption that the prescribed agent also will be effective in reducing symptoms of comorbid depression, the majority of studies have failed to find a strong relationship between depression symptoms and headache improvement. Suggestions for future research are discussed.     

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.     

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.     

Dramatic remission of treatment-resistant depression after the cessation of tricyclic antidepressants

Recently, tricyclic antidepressants (TCAs) have been used mainly for treatment-resistant depression (TRD) because of their significant side effects . We report a patient whose prolonged depressive symptoms dramatically improved after the cessation of TCAs. TCAs may cause deterioration of depressive symptoms due to their neurotoxicity.     

Prevalence,clinical features and treatment of depression in Parkinson’s disease: An update

Parkinson’s disease (PD) is one of the most prevalent neurodegenerative diseases which typically affects individuals over 65 years. Although the symptomatology is predominantly motor, neuropsychiatric manifestations, e.g., depression, apathy, anxiety, and cognitive impairment occur in the course of the illness and can have a great impact on the quality of life in these patients. Parkinson’s disease is commonly comorbid with depression with prevalence rates of depression, generally higher than those reported in general population. Depression in PD is frequently underestimated and consequently undertreated, which have significant effects on the quality of life in these patients. The neurobiology of depression in PD is complex and involves alterations in dopaminergic, serotonergic, noradrenergic and possibly other neurotransmitter systems which are affected in the course of the disease. The tricyclic antidepressants and the selective serotonin reuptake inhibitors are the two classes of antidepressant drugs used for depressive symptoms in PD. Several published studies suggested that both classes are of comparable efficacy. Other serotonergic antidepressants, e.g., nefazodone and trazodone have also been of benefit. Meanwhile, there are limited data available on other drugs but these suggest a benefit from the serotonin and noradrenaline reuptake inhibitors such as mirtazapine, venlafaxine, atomoxetine and duloxetine. Some of the drugs used in symptomatic treatment of PD, e.g., the irreversible selective inhibitors of the enzyme monoamine oxidase-B, rasagiline and selegiline as well as the dopamine receptor agonist pramipexole are likely to have direct antidepressant activity independent of their motor improving action. This would make these drugs an attractive option in depressed subjects with PD. The aim of this review is to provide an updated data on the prevalence, clinical features of depression in subjects with PD. The effects of antiparkinsonian and antidepressant drugs on depressive symptoms in these patients are also discussed.     

Use of Antidepressants in Treatment of Comorbid Diabetes Mellitus and Depression as Well as in Diabetic Neuropathy

After a brief review of epidemiology, the focus is on biochemistry of diabetes. Animal and human studies are reviewed in terms of the impact of alterations in catecholamines and serotonin (5-hydroxytryptamine, 5HT) on glucose utilization. Then, the implications of these experimental results for the choice of antidepressant in comorbid diabetes mellitus and depression as well as in diabetic neuropathy are discussed. Results of clinical investigations are then reviewed in terms of the above hypotheses. An Index Medicus Search for the past 10 years was supplemented by references from previous related reviews of the topic as well as by pending results, where available, not previously published. The range of prevalence of depression in diabetic patients has been 8–27%, depending on study criteria and procedures. An increase of catecholamines appears to increase glucose while both reducing insulin release and reducing sensitivity to insulin that is available. In contrast, increases in serotonergic function by increased precursor, increased release, or blocked metabolism and blocked reuptake in contrast seem to increase sensitivity to insulin and reduce plasma glucose. There have been six studies of fluoxetine, a selective serotonin reuptake inhibitor (SSRI), at a dose of 60 mg/day pursued up to 12 months that have demonstrated that medication's usefulness in diabetic patients, with reductions in weight (to 9.3 kg), in FPG (to 45 mg%), and in HbA1c (to 2.5%). In studies in comorbid diabetes mellitus and depression, nortriptyline, a norepinephrine reuptake inhibitor that produces increased synaptic catechols, has led to worsening of indices of glucose control. However, fluoxetine and sertraline, both selective serotonin reuptake inhibitors, in the same patient group, have produced results consistent with reductions in glucose levels. In diabetic neuropathy, perhaps due to the fact that catecholamines and serotonin may both be implicated in pain pathways, dual-action antidepressants appear more effective at lower doses than do specific serotonergic agents. The tricyclic antidepressants (TCA) (66.7%) have had success in double-blind studies, particularly imipramine, with a 81% response rate. Yet, there are positive reports concerning the SSRIs (paroxetine, citalopram, sertraline), as well as nefazodone, that focus on serotonin selectivity. Conclusions: In comorbid diabetes mellitus and depression, most evidence supports the use of fluoxetine in control of glucose handling. Other characteristics in terms dosing, drug interactions, cognition, and sleep make sertraline an attractive alternative agent. In diabetic neuropathy without depression, the best choices among non-TCAs may include sertraline, citalopram, and perhaps, venlafaxine, since the TCAs appear to increase cravings and increase FBG levels.     

Prevalence,clinical features and treatment of depression in Parkinson's disease: An update

Parkinson's disease(PD) is one of the most prevalent neurodegenerative diseases which typically affects individuals over 65 years. Although the symptomatology is predominantly motor, neuropsychiatric manifestations, e.g., depression, apathy, anxiety, and cognitive impairment occur in the course of the illness and can have a great impact on the quality of life in these patients. Parkinson's disease is commonly comorbid with depression with prevalence rates of depression, generally higher than those reported in general population. Depression in PD is frequently underestimated andconsequently undertreated, which have significant effects on the quality of life in these patients. The neurobiology of depression in PD is complex and involves alterations in dopaminergic, serotonergic, noradrenergic and possibly other neurotransmitter systems which are affected in the course of the disease. The tricyclic antidepressants and the selective serotonin reuptake inhibitors are the two classes of antidepressant drugs used for depressive symptoms in PD. Several published studies suggested that both classes are of comparable efficacy. Other serotonergic antidepressants, e.g., nefazodone and trazodone have also been of benefit. Meanwhile, there are limited data available on other drugs but these suggest a benefit from the serotonin and noradrenaline reuptake inhibitors such as mirtazapine, venlafaxine, atomoxetine and duloxetine. Some of the drugs used in symptomatic treatment of PD, e.g., the irreversible selective inhibitors of the enzyme monoamine oxidase-B, rasagiline and selegiline as well as the dopamine receptor agonist pramipexole are likely to have direct antidepressant activity independent of their motor improving action. This would make these drugs an attractive option in depressed subjects with PD. The aim of this review is to provide an updated data on the prevalence, clinical features of depression in subjects with PD. The effects of antiparkinsonian and antidepressant drugs on depressive symptoms in these patients are also discussed.     

Treatment of severe depression with the selective serotonin reuptake inhibitors

The selective serotonin reuptake inhibitors (SSRIs) are recognized as effective as and better tolerated than older antidepressant therapies and have become the drugs of choice in the treatment of mild to moderate depression. However, there is a clinical impression that the SSRIs are less effective than older therapies in the severely depressed patient. A limited number of trials have attempted to address this issue. This review assesses 16 controlled studies of SSRIs in severe depression. The findings from a majority of studies found the SSRIs to be superior to placebo and as effective as but better tolerated than the tricyclic antidepressants (TCAs) in severely depressed patients. Although future studies are needed to corroborate and elaborate on these data, studies still support the use of SSRIs in this patient population. Depression and Anxiety 4:182–189, 1996/1997. © 1997 Wiley-Liss, Inc.     

The effects of antidepressants in Parkinson's disease: a meta-analysis

This study explored the therapeutic effect of antidepressants in Parkinson's disease (PD) using a meta-analysis. Altogether, 24 placebo-controlled trials qualified for inclusion and revealed that tricyclic antidepressants (TCAs) had a greater antidepressant effect relative to selective serotonin reuptake inhibitors (SSRIs), Qb(1) = 8.87, p < .01, and the mono-amine-oxidase inhibitor, selegiline, Qb(1) = 7.90, p < .01. Whereas TCAs produced a significant side effect profile (odds ratio = 3.07), adverse events were negligible with SSRIs (odds ratio = 1.83) and selegeline (odds ratio = 1.63). Antidepressants can be beneficial for patients with PD. However, the choice of antidepressants needs to take depressive symptomatologies into account while monitoring side effects.     

Adjunctive lithium treatment in the prevention of suicidal behavior in patients with depression and comorbid personality disorders

Objective. Patients with both major depression and personality disorders have a high risk of suicidal behavior. Lithium is meant to have anti-suicidal properties in patients with affective disorders. The anti-suicidal effect of lithium in patients with affective disorders and comorbid personality disorders has not been investigated yet. Methods. A post-hoc analysis of a subsample of patients with depression and comorbid personality disorder (PD) and a recent suicide attempt (n = 19) from the prospective, placebo-controlled lithium intervention study (N = 167), was conducted. Results. Three patients in the lithium group (n = 8) and two patients in the placebo group (n = 11) presented a suicide attempt throughout the course of the study. No differences related to suicidal behavior could be detected between the placebo group and the group with lithium intervention. Conclusions. On the basis of the small sample size, among patients with comorbid PD, lithium does not seem to have an effect on suicidal behavior in contrast to patients with affective disorders without comorbid PD.     

Monoamine oxidase inhibitors. A review of antidepressant effectiveness.

Data from double-blind, placebo-controlled trials of the monoamine oxidase (MAO) inhibitors show that phenelzine is clearly effective in neurotic or atypical depressives, but the findings concerning its effect in endogenous depressives are inconclusive. Although few controlled studies have been done with tranylcypromine, similar conclusions are warranted. Studies have contrasted MAO inhibitors and tricyclic antidepressants (TCAs) to gain further information about the type of patients likely to respond to MAO inhibitors. We believe that simply contrasting the relative efficacy of TCAs and MAO inhibitors is outdated. Neurotic or atypical depression is probably a heterogeneous syndrome, and delineation of subtypes responsive to specific antidepressants is needed. The implications of fast acetylation, selective MAO inhibitors, types MAOA and MAOB, and measures of platelet MAO inhibition are discussed in this article.     

Paroxetine for somatic pain associated with physical illness: a review

Objective: The purpose of this article is to review the prevalence of somatic pain with and without depression or anxiety and the pharmacologic effects of the selective serotonin reuptake inhibitor paroxetine on pain in physical conditions with and without comorbid depression or anxiety. Data Sources: MEDLINE and PsychLIT/PsycINFO database. Keywords included depression, anxiety, pain, somatic, antidepressants, and paroxetine. Only English-language publications and abstracts were considered. Study Selection: More than 100 articles that reflected the prevalence of somatic pain in patients with physical illness with and without comorbid depression or anxiety and that evaluated the efficacy of antidepressants in this population were identified and reviewed. Data Synthesis: Nearly two thirds of patients with major depressive disorder suffer from a physical illness, and about one fifth of patients with chronic physical illness are depressed. Both of these comorbidities pose diagnostic and therapeutic challenges. Therapeutic effects of antidepressants on pain improvement in patients with chronic physical illnesses and comorbid depression/anxiety have been attributed to the antidepressant or anxiolytic properties of these drugs. However, tricyclic antidepressants have demonstrated analgesic properties in patients with physical illness both with and without depression. The review looks at evidence for the efficacy of the selective serotonin reuptake inhibitor paroxetine on pain in physical illness with and without depression and the mechanisms for the relief of pain and depression. Conclusions: The efficacy of paroxetine for depression and anxiety comorbid with physical illness looks promising. Studies also allude to evidence linking the analgesic properties of paroxetine with its serotonergic and noradrenergic activity. Large randomized controlled trials within specific antidepressant classes and also comparing dualaction antidepressants are warranted that could shed some light on the unique advantage of paroxetine over other antidepressants.     

Depression in the medically ill: Management considerations

This article reviews the management of depression in three medical conditions associated with a high frequency of depression: coronary artery disease (CAD), cancer, and human immunodeficiency virus (HIV) infection. Major depression significantly increases mortality in patients with CAD. This effect of depression may be mediated by a decrease in heart rate variability. Tricyclic antidepressants (TCAs) possess Type 1A antiarrhythmic activity, which may increase the risk of sudden death. Initial data suggest that tricyclic antidepressants also may decrease heart rate variability. Antidepressant therapy is effective and can improve quality of life for patients with cancer or HIV infection. Strong social support or psychosocial interventions that improve coping skills may positively affect outcome in HIV infection and cancer. Selective serotonin reuptake inhibitors(SSRIs) and new agents may be well suited for use in depressed patients with medical illnesses because they lack the significant adverse anticholinergic and cardiovascular effects of TCAs and other classes of antidepressants. Depression and Anxiety 4:199–208, 1996/1997.© 1997 Wiley-Liss, Inc.     

SSRI efficacy-finding the right dose

The selective serotonin reuptake inhibitors (SSRIs) are a class of effective, well-tolerated antidepressants. They have a number of benefits compared with the tricyclic antidepressants (TCAs) including improved safety in overdose, reduced side-effect burden, and uncomplicated dosing regimens. To avoid the potential for troublesome side effects with TCAs, doses should be gradually increased over several weeks. Dose titration can be associated with several drawbacks such as patients discontinuing therapy due to a prolonged time to therapeutic response, additional visits to a prescribing healthcare provider, or additional hospitalizations. In contrast, the SSRIs typically do not require dose titration since many patients find the initial dose effective. The ability to prescribe an initial optimum therapeutic dose while avoiding dose-related side effects is important in the treatment of major depression. With this in mind, the authors consider the recommended dose ranges for the five SSRIs: citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline.     

The effectiveness of antidepressants in the treatment of chronic non-cancer pain--a review

Antidepressants are often applied in the treatment of chronic pain. Analgesic action of tricyclic antidepressants (TCAs) has been extensively studied and proven. TCAs are associated with a number of adverse effects which are inconvenient for patients. The newer antidepressants have fewer side effects and equivalent efficacy on mood disorders. This article reviews the available publications (mainly placebo-controlled trials) concerning the efficacy of these medications in the treatment of chronic pain. The data regarding selective serotonin reuptake inhibitors (SSRI) are conflicting. Trazodone (a serotonin-reuptake inhibitor as well as a postsynaptic serotonin receptor antagonist) does not appear to be effective for the treatment of chronic pain. No placebo-controlled studies are available for noradrenergic and specific serotoninergic antidepressant (NaSSA)--mirtazapine and noradrenaline reuptake inhibitor (NaRI)--reboxetine. Bupropion, a noradrenaline and dopamine-reuptake inhibitor appears to be effective in the treatment of neuropathic pain. Venlafaxine--selective serotonin and noradrenergic reuptake inhibitors (SNRI) was shown to be effective in the treatment of different kinds of pain. Duloxetine (SNRI) is effective in relieving both the emotional and painful physical symptoms of depression. Additional randomized, controlled trials are necessary to fully evaluate the role of new antidepressants in the treatment of chronic pain.