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Depression and diabetes mellitus 

Depression and diabetes mellitus
Chapter:
Depression and diabetes mellitus
Author(s):

Khalida Ismail

and Frank Petrak

DOI:
10.1093/med/9780199235292.003.1574
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Introduction

There is a high prevalence of co-morbid depression in people with diabetes. Depression is a mental disorder that is associated with worse physical outcomes in diabetes, in particular higher rates of diabetes complications and mortality, but it is often undetected and undertreated. The mechanisms underlying the high rates of depression and its adverse effects are not well understood but appear to include both biological and psychological processes. Depression may have a more chronic course in people with diabetes compared to those without diabetes. The current evidence for the treatment of depression in diabetes suggests that treating depression improves mood but its effectiveness in improving glycaemic control is poor.

Characteristics of depression

Clinical depression is a pervasive and persistent lowering of mood. It is a dimensional (or continuous) construct of psychological functioning but it can also be categorised by the number, type (core or associated) and severity of depressive symptoms (see Fig. 13.8.1.1).


Fig. 13.8.1.1 The dimensional and categorical nature of depression using the definition of a major depressive episode in the Diagnostic and Statistical Manual of Mental Disorders (4th edition).

Fig. 13.8.1.1
The dimensional and categorical nature of depression using the definition of a major depressive episode in the Diagnostic and Statistical Manual of Mental Disorders (4th edition).

According to the World Health Organization’s International Classification of Diseases, 10th revision (ICD-10) criteria, a diagnosis of a depressive episode requires that an individual has experienced at least two out of the three core (low mood, anhedonia, and fatigue) symptoms and at least two out of the seven associated symptoms (see Table 13.8.1.1) (1). The Diagnostic and Statistical Manual for Mental Disorders 4th edition (DSM-IV) has similar criteria (Table 13.8.1.1) for the diagnosis of major depressive disorder, except that an individual has to experience at least one of two core symptoms (low mood and anhedonia) and a minimum of five symptoms in total (2). The clinician decides which classification to use but, in both, symptoms need to be present for most of the day and nearly every day for a minimum of 2 weeks. Severity depends on the number and intensity of associated symptoms (see Fig. 13.8.1.1).

Table 13.8.1.1 Comparison of the criteria for depressive disorder in the two most common classifications for mental disorders

International Classification of Diseases -10

Diagnostic and Statistical Manual for Mental Disorders-4th edition

Core symptoms

Core symptoms

Low mood

Low mood

Anhedonia

Anhedonia

Fatigue

Associated symptoms

Fatiguel

Insomnia or hypersomnia

Insomnia or hypersomnia

Change in appetite with corresponding weight changes

Change in appetite with corresponding weight changes

Diminished concentration

Diminished concentration

Recurrent thoughts of death or suicidal ideas ideation

Recurrent thoughts of death or suicidal ideas ideation

Excessive guilt or worthlessness

Excessive guilt or worthlessness

Psychomotor agitation or retardation

Psychomotor agitation or retardation

Loss of confidence or self esteem

Minimum criteria for diagnosis of depression

Minimum criteria for diagnosis of depression

At least 2 core symptoms and 2 associated symptoms

At least 1 core symptom and 5 symptoms in total

The gold standard for assessing depression is the clinical interview. Many general health professionals perceive that they lack the interview and consultation skills to assess mood. Yet this is relatively straightforward with simple techniques that should always start with open questions about each of the core symptoms, such as ‘During the past month, how would you describe your mood?’ and ‘During the past month, how often have you been bothered by having little interest or pleasure in doing everyday things?’. After a positive response, it is important to ask about the duration and intensity of the symptoms and to exclude active suicidal ideation.

Three of the most commonly used self-report questionnaires used for screening for depression in diabetes settings are the Patient Health Questionnaire-9 (PHQ-9) (3); the Hospital Anxiety and Depression Scale (4); and the Center for Epidemiologic Studies Depression Scale (5). The screening questionnaire should not be used as substitute for interviewing the patient and questionnaires should not be used to make a diagnosis of depression and to make decisions about treatment, as they tend to have low specificity.

There are structured and semi-structured diagnostic interviews such as the Composite International Diagnostic Interview (6), the Schedule for Clinical Assessment in Neuropsychiatry (7), and the Structured Clinical Interview for DSM-IV Disorders (8). These are mainly used for research purposes. Their advantage over self-report screening questionnaires is that clinical judgement about the nature and aetiology of the depressive symptoms are taken into consideration when rating their presence and severity. This results in lower and more valid prevalence rates for clinical depression. Semi-structured interviews are also very useful as training material for developing consultation skills for assessment of mood.

Common differential diagnoses for depression are other psychiatric conditions (adjustment disorder, bereavement reactions, alcohol and substance misuse, longstanding personality traits) and organic or medical conditions such as a dementing process, thyroid disease, Addison’s disease and other endocrine or autoimmune disorders. It is also important to recognize that symptoms of depression such as low mood and fatigue can sometimes be a feature of persistent suboptimal glycaemic control (recurrent hypoglycaemia, persistent hyperglycaemia) and biological changes from diabetes complications such as gastroparesis, making the diagnosis of an underlying clinical (functional) depression more difficult for the unwary.

Epidemiology of depression in diabetes

Prevalence of depression

People with diabetes are twice as likely to have depression compared with the general population, with a pooled prevalence of 9% for depressive disorders based on diagnostic interviews and 26% based on self-report scales in controlled studies (9, 10). It seems that there is little difference in the prevalence of depression between type 1 and type 2 diabetes but there have not been enough well-designed studies to test this hypothesis (911). Considering that the aetiology, epidemiology, and treatment of type 1 and type 2 diabetes are different, more research is needed to ascertain whether the risk factors, nature, and treatment of depression might also vary between the two types of diabetes.

Depression is consistently associated with a 37–60% increased risk of type 2 diabetes (12, 13). This has led to suggestions that depression could be an independent risk factor for type 2 diabetes but alternative explanations such as the misclassification of symptoms of undiagnosed diabetes and residual confounding (both depression and type 2 diabetes are conditions associated with lower socioeconomic status) need to be excluded. Little is known about the prevalence of depression in newly diagnosed type 2 diabetes, which is an obvious opportunity for interventions to improve both biomedical and mental health outcomes. In adults with type 1 diabetes there is some evidence that depression rates are increased within 6 months of diagnosis for females but not for males (14).

Course of depression

Unlike type 2 diabetes, depression does not deteriorate progressively and there are, as yet, no specific biological diagnostic markers. Depression can completely or nearly completely remit, have a relapse-remitting course or a chronic course. Factors associated with recurrence and chronicity are prior history of depression, severity of depression, co-existing anxiety, concurrent medical conditions, and partial treatment of depression. Even less is known about the course of depression in diabetes, although the suggestion from a handful of highly selected diabetes patients is that it is more likely to recur and to be chronic (15, 16).

Impact of depression

People with depression in diabetes have worse outcomes. They have worse quality of life (17) than those having diabetes alone, hence the term ‘doubly disabled’; they have increased health care costs (18); they have worse quality of health care (19); and are less likely to adhere to diabetes self-care (18, 19). There is also a common view that depression is associated with worse glycaemic control, yet when the studies, most of which are cross-sectional, are pooled, the size of this association is smaller than expected (pooled effect size of 0.17) (20). A recent study from the Whitehall Study of UK civil servants found a curvilinear association with lower and higher fasting bloods and HbA1c associated with self-reported depressive symptoms (21). In the handful of prospective studies, depression is not associated with worse glycaemic control (e.g. Ismail et al. (22), Fisher et al. (23), and Aikens et al. (24)), except in a US study of older male veterans, which observed a small effect (25). Until more longitudinal data emerge, the evidence base for the view that depression leads to significantly worse glycaemic control over time is unclear.

Depressed people tend to have more diabetes-related symptoms (26) and to be on insulin (27). There is a small to moderate increase in the prevalence rates of depression in those with diabetes complications compared to those without complications (22, 28). The most worrying finding (22, 29), is that depression in diabetes is associated with a two- to five-fold increase, with the higher risks in the elderly, in all-cause mortality, mostly cardiovascular. Similar findings have been observed in studies of depression and mortality following myocardial infarction and there are smaller but significant independent associations between depression and mortality in the general population.

Risk factors for depression

In the general population, risk factors for the onset of depression include life events such as death of the mother in childhood, marital separation in adult life, and childhood neglect and abuse of any type (emotional, physical and sexual); lack of social support; female gender; genetic factors; and low socio-economic status. The extremes of the adult lifespan (younger and older adults) are at increased risk compared with those in mid-life. Life events are important precipitants for the first episode but less so with subsequent episodes of depression, which is supposed to represent a ‘kindling’ effect of depression.

Although there have not been many controlled studies to compare whether the risk factors associated with depression in the general population also apply to those with diabetes and depression, it is reasonable to assume this (19). Ethnicity (which includes myriad of concepts such as cultural beliefs and behaviours, migration status, perceived and objective accessibility to diabetes care, language, religion, and genetics) has face validity as an important factor but the evidence, mostly from the US, is not straightforward (19). There are factors that are specific to diabetes. People with complications have an increased risk for depression compared with those without (28) and both insulin treatment and delays in its uptake seem to be associated with depressive symptoms (30, 31).

Associated psychiatric and psychological morbidity

Depression often co-exists with nearly all the major categories of psychiatric disorder, including the dementias, psychosis, anxiety disorders, eating disorders, and personality disorders. Depression is a common prodromal state of the early stages of dementia either as an epiphenomenon of having insight into one’s own cognitive deterioration and/or as a consequence of cerebrovascular changes. It is important to assess mood as a differential diagnosis and as a comorbid condition if there is deterioration in cognitive functioning.

Anxiety has two core features: cognitions (thoughts) of pervasive and excessive worry or fear (which in phobias is a fear of a situation or a specific object such as a needle) and an associated autonomic arousal response which can mimic hypoglycaemia. Estimates of co-morbidity of anxiety and mood disorders in the general population vary from 25% to 50% or more and is associated with worse depressive outcomes. In people with diabetes, a pooled prevalence of 14% for generalized anxiety disorder has been reported (32). Recent controlled studies indicate that there is a 20% increased risk for lifetime prevalence of anxiety disorders in patients with diabetes (33, 34). Fear of self-injecting insulin and self-testing of blood glucose, and fear of complications are well-recognized clinical entities (35) that are related to the anxiety spectrum.

Depressive symptoms commonly occur in eating disorders (2). As eating problems are more common in people with diabetes than controls (2, 36) it is important to assess mood and treat it if depressed. In anorexia, depression may be partly a physiological manifestation of starvation but in bulimia and binge eating disorder, depression is more likely to be a comorbid condition. People with diabetes have high levels of emotional distress stemming from concerns and worries associated with their diabetes and its management, and this state is to be distinguished from depression. It is variously labelled as diabetes distress, diabetes specific problems and worries, diabetes burnout, or problem areas in diabetes. There are strong correlations with depressive symptoms (23). The utility of the diabetes distress construct as a valid prognostic indicator and screening tool for problematic diabetes control compared to depression is promising.

Psychological mechanisms

The conventional explanation for the adverse association between depression and diabetes has been the psychological model. This purports that people who have diabetes are more likely to get depressed because first, they have the emotional burden or threat of living with a lifelong and progressive condition and, second, they have to adapt to a new role involving multiple diabetes self-care behaviours such as increasing physical activity, changing their diet, checking blood glucose, feet, and weight, and taking medication. Low mood, loss of interest, loss of self-worth and tedium vitae mediate the reduced diabetes self-care. In cross-sectional studies, depression is associated with reduced diabetes self-care, which can lead to poor glycaemic control and this has been substantiated in a recent prospective study (38). Progression of disease leads to increased disability, and further changes in social roles may explain why higher rates of depression are observed in those with tissue complications (22, 28). In the Multi-Ethnic Study of Atherosclerosis, in a cohort of US adults aged 45–84 years enrolled in 2000–2002 and followed up until 2004–2005, only a small association between baseline depression and incident type 2 diabetes was observed. In addition, impaired fasting glucose and untreated type 2 diabetes were inversely associated with incident depressive symptoms, whereas treated type 2 diabetes showed a positive association with depressive symptoms (39). In a mostly type 2 sample, those taking insulin have more depressive symptoms than those on diet or oral medication (30). Both these studies suggest that it is the emotional and practical burden of managing diabetes as it progresses that mediates the depression–diabetes link.

The psychological model does not fully explain the adverse effects of depression. The association between depression and glycaemic control is small if present at all, suggesting that the effect of depression cannot be solely explained by its mediating effects on diabetes self-care. In a prospective cohort of first onset of diabetic foot ulcers, depression was associated with higher mortality rates, even after adjusting for macrovascular complications and HbA1c (22). There is little evidence from randomized controlled trials (RCTs) that treating depression in diabetes improves glycaemic control, although the treatments do improve mood (40). Recently some investigators have proposed that it is the thoughts and feelings related to the diagnosis and living with diabetes, in other words diabetes distress, that is the important prognostic factor for poor diabetes outcomes (23) rather than clinical depression per se. These findings suggest that the co-morbidity of depression and diabetes is not mediated solely by emotions and behaviours and additional mechanisms, such as biological processes, need to be considered. Whether the psychological model is more relevant to type 1 than to type 2 diabetes is not yet known but the onset of type 1 diabetes, typically during developmental phases, probably has a larger impact on personality development and family functioning than onset of type 2 diabetes in mid-life when personality consists of mostly entrenched traits. This may change as type 2 diabetes occurs in younger age groups.

Similar limitations of the psychological model have been observed in people with depression and coronary heart disease, which is relevant as type 2 diabetes and cardiovascular diseases share a common causal pathway (41). It is well-known that depression, including persistent depression, is associated with increased mortality rates in people with coronary heart disease. Yet depression appears to explain only a third of the variance in adherence to cardiovascular medication and in RCTs of treatments (antidepressant or psychotherapy) for depression in people who have had acute cardiac events, mood usually tends to improve usually without significant improvement in cardiovascular outcomes.

Biological mechanisms

There are several biological processes that could at least in part account for the diabetes–depression link. These include the hypothalamic–pituitary–adrenal axis (HPA), the inflammatory response, insulin resistance, cognitive impairment, and developmental perspective.

Acute stress (the flight-fright response, acute anxiety, shock) is associated with autonomic arousal as manifested by sympathoadrenal activation, activation of the HPA and the hypothalamic–growth hormone axes. These lead to gluconeogenesis, glycogenolysis, and insulin resistance, which is an adaptive response to threat. Clinical depression is sometimes described as a chronic (possibly abnormal) stress state. There have been many studies demonstrating that levels of glucocorticoids, in particular, cortisol, are increased in severe depression but this has been a less consistent finding in subthreshold, minor and moderate depressive disorders. The utility of the HPA axis as a biological marker for depression has not to date been successful.

A potential explanation for the diabetes–depression link is that depression is associated with a cytokine-induced acute-phase response, a biologically plausible hypothesis first proposed in 1991 as ‘the macrophage theory of depression’ (42). The acute-phase response and innate immunity is also closely involved in the pathogenesis of type 2 diabetes, as first proposed by Pickup and Crook in 1998 (41).

Production of pro-inflammatory cytokines and the acute phase response are associated with pancreatic β‎-cell apoptosis, reduced insulin secretion, insulin resistance, onset of type 2 diabetes, and worse cardiovascular prognosis (43). There is growing evidence that the acute phase response is also associated with depression. A recent systemic review summarized the current evidence for the cross-sectional correlation between C-reactive protein (CRP), interleukin (IL)-1, 1L-1ra, and IL-6 and depression in the general population, and in those with cancer and heart disease (44). The associations are generally smaller than seen in type 2 diabetes but are stronger in clinically depressed samples compared with community samples and for those that used clinical interviews versus self-report measures of depression. Studies that included confounding, such as body mass index, increasing age, sex, use of statins, antidepressants and anti-inflammatory agents, improved the validity of individual studies but gave more inconclusive results. Prospective studies in coronary heart disease have found that depression is correlated with levels of inflammatory markers and both factors are associated with worse cardiac outcomes. To date, there have been no prospective studies of the bi-directional association between inflammatory markers and depression in diabetes.

A dilemma in studying the pathogenesis of the depression–diabetes link in type 2 diabetes is deciphering the ‘chicken or egg’ causal pathways. To date, associations seem to be generally bidirectional, suggesting that this approach maybe not valid. The notion that depression and type 2 diabetes may have common origins is a more promising one that may one day lead to novel targets that treat both. Low birthweight (a marker of fetal nutrition) is associated with depression (45), and with impaired glucose tolerance (46) in adult life and these observations have been replicated. In the Helsinki Birth Cohort Study, low birthweight was associated with more than a doubling of the risk for depressive symptoms and modified the association between coronary heart disease and diabetes with depression (47).

There are several studies now demonstrating cross-sectional associations between insulin resistance and depression, although not all are affirmative (48, 49). Prospective evidence is awaited. There is a growing consensus that depression increases the risk of obesity (50). More studies using life-course epidemiology are needed to identify the relative independent effects of factors, and their interactions, across the lifespan, on depression and type 2 diabetes endpoints.

Treatment of depression

Considering the significant evidence base that depression has an adverse effect on psychological and diabetes outcomes, treatment of depression in diabetes should be directed toward improving both. Treatment depends on the identification and severity of depression. For this chapter, we will use the UK guidelines as a model (51) (Fig. 13.8.1.2) of one of the few to include chronic physical health, but other diabetes specific guidelines exist.


Fig. 13.8.1.2 NICE guidelines for depression in adults.

Fig. 13.8.1.2
NICE guidelines for depression in adults.

Screening and diagnosis

Patients with depression are often unaware that their symptoms are related to a depressive disorder. In consultations with their doctor they often communicate non-specific physical symptoms and minimize the psychological symptoms. The general practitioner (GP) plays a key role in recognizing early that depression is a differential diagnosis. In screening questions for depression, the GP or hospital physician should enquire about core symptoms (depressive mood, loss of interest and pleasure in activities and/or reduction in energy and drive depending on the classification being used). The first two questions of the PHQ-9 (labelled the PHQ-2), although brief at 1 min and sensitive at 96%, is not specific at 57% (52). The full PHQ-9 has a specificity of 90%.

Treatment

Improvement of depressive symptoms or remission is the major mental health outcome target. The medical treatment targets include an improvement of glycaemic control, a reduction of risk for short- and long-term complications, and premature mortality. For an overview of current knowledge, all published RCTs that evaluated treatment of depression in diabetes were grouped according to the interventions that were used.

Pharmacological treatment trials

In the first published RCT, nortriptyline was compared with a placebo in patients with depression and poorly controlled diabetes. Depression significantly improved in the nortriptyline group, but a deterioration of glycaemic control was observed in the intervention group in subsequent analyses (55). The next trial evaluated the effectiveness of fluoxetine compared with a placebo in diabetes patients with depression. Again, there was a significant improvement in depression after 2 months of treatment in the intervention group but no statistically significant differences were observed between the treatment groups regarding glycaemic control (56). A more recent RCT evaluated the effect of sertraline on prevention of relapse of depression in diabetes patients (57). Responders of a non-controlled, open-label treatment with sertraline were subsequently included in a RCT for a maximum of 12 months comparing sertraline to a placebo for relapse prevention. Patients treated with sertraline had a significantly longer time to recurrence of depression compared with placebo. Regarding glycaemic control, there was a significant improvement in the whole sample in the non-randomized phase of the study when every participant was administered antidepressant but no further advantage of sertraline could be observed in the RCT phase of this trial. Finally, paroxetine was compared with a placebo in elderly patients with minor depression (58). The results yielded no statistically significant differences between the groups on the primary psychological and medical outcome variables.

Psychological treatment trials

The only published trial of cognitive behavioural therapy (CBT) included 52 patients with type 2 diabetes and major depression (59). Patients were randomized to diabetes education and CBT for depression or to diabetes education only. The follow-up included a six-month interval during which 70% of the patients in the CBT group achieved remission of depression compared with just 33% in the education-only group. Regarding HbA1c, there was a statistically and clinically significant advantage of CBT compared with the control group 6 months after treatment was delivered. A further RCT comparing group counselling with 59 patients to treatment as usual was conducted in China (60) and demonstrated significant improvements for the group counselling condition for both depression and glycaemic control. The most recent trial was a pilot study to evaluate supportive psychotherapy in patients with diabetic foot syndrome who had depressive symptoms (61). Patients were randomized to either supportive psychotherapy or standard medical treatment. Results, which were reported for post-treatment evaluation but not for follow-up data, demonstrated a moderate improvement for depressive symptoms, but no significant difference was observed for glycaemic control or other medical outcome variables.

Combined psychological and pharmacological treatments

The effectiveness of algorithm-based, flexible interventions using a combination of psychological and pharmacological treatments compared with standard care was evaluated in four RCTs. The psychological modules of these treatments included problem-solving training (62, 63) and counselling (64) or interpersonal therapy (65). In addition, in all four trials, antidepressants were given according to the patients’ preferences or following a pre-defined treatment algorithm. A significant improvement in depression was observed for the combination of antidepressant medication with problem-solving training (62, 63) or counselling (64) compared with standard care. However, no significant differences between the intervention and control groups were observed in metabolic control.

In an algorithm-based care trial that included 123 patients with depression and self-reported diabetes (among 584 patients without diabetes), interpersonal therapy and citalopram (in combination or alone) were compared with care as usual (65). The results of a secondary analysis demonstrated that this intervention led to a significant decrease in mortality after five years. As diabetes status was based on self report, no conclusion can be drawn regarding the effectiveness of depression treatment on mortality.

Finally, a recent RCT was conducted in which diabetes patients with depression were randomized to a so-called multi-faceted psychiatric intervention or to usual care (64). The intervention group was given the options of counselling, a case conference, or referral to a psychiatrist. Antidepressant medication was an option in all treatment conditions. The results were significantly better for the intervention group regarding depression but no positive effect on medical outcome was observed.

A generic model for the treatment of depression in diabetes

A generic algorithm can be adapted to the local setting to structure the treatment of depression in diabetes as shown in Fig. 13.8.1.2 and Fig. 13.8.1.3.


Fig. 13.8.1.3 A generic algorithm for the treatment of depression in diabetes. SSRI, selective serotonin reuptake inhibitor.

Fig. 13.8.1.3
A generic algorithm for the treatment of depression in diabetes. SSRI, selective serotonin reuptake inhibitor.

Subclinical or a mild depression

If the patient is not suicidal, there is no acute crisis, and prior attempts at therapy were not a failure, then the attending physician can administer basic treatment in order to reduce symptoms. This treatment encompasses the following:

  • building a trusting relationship with the patient

  • providing information about depression

  • conveying encouragement

  • relieving feelings of blame

  • accepting the patient’s behaviour (including complaining)

  • positively reinforcing nondepressive cognitions

  • anticipating the patient’s vulnerability

  • activating and motivating the patient without overwhelming him or her

  • taking notice of, and addressing suicidal tendencies

Monitoring for improvement is recommended after 2 weeks. If there is no improvement, the next step of the algorithm, which is also the starting point for moderate depression, should be taken.

Moderate depression

A specific treatment regimen is recommended and includes medication or psychotherapy or a combination of both. If no improvement occurs after approximately 4 weeks, the next step of the algorithm, which is also the starting point for treatment for severe depression, should be started.

Severe depression

An enhanced treatment regimen specific therapy (antidepressant medication with, or followed by, psychotherapy) is recommended in specialized care. This is usually outpatient care but may be as an in-patient.

In all steps of the algorithm, a continuous monitoring focusing on response, side effects, and achievement of medical goals is recommended.

There are three main categories of antidepressants: tricyclics, selective serotonin reuptake inhibitors (SSRIs) and a mixed group that include serotonin and noradrenergic reuptake inhibitors (SNRIs) such as venlafaxine, presynaptic α‎2-adrenoreceptor antagonists such as mirtazapine, and monoamine oxidase inhibitors. When selecting an antidepressant for patients with diabetes, SSRIs are usually the first choice as they are as efficacious as tricyclic antidepressants, they are better tolerated and less likely to lead to weight gain and glycaemic changes (although the latter statement is based on very limited data). Switching antidepressants is best conducted in consultation with a psychiatrist. Once a patient is in remission, antidepressants should be continued for at least 6–9 months and for those with recurrent depression, prophylactic sertraline has been shown to reduce relapses in diabetes (16). Tricyclic antidepressants, especially amitriptyline, do have a specific role in diabetes as an analgesic for painful peripheral neuropathy, when they may be the preferred antidepressant of choice if used at therapeutic doses for the treatment of depression. Mirtazapine may be a preferred first choice in those with diabetic gastroparesis as it has an anti-emetic effect. In a recent systematic review, anti-depressants, mirtazapine, escitalopram, venlafaxine, and sertraline were more effective when compared to fluoxetine (66).

Research gaps in depression treatment for patients with diabetes

Little is known of the mechanisms of action for positive treatment effects; better knowledge, especially of the underlying pathogenesis of the depression–diabetes link, could stimulate the development of new treatment options. We need to learn more about the usefulness of specific interventions. Regarding pharmacological treatments, the question remains as to whether better biomedical outcomes for variables would be possible through the use of other medications. With respect to combined treatments, we do not know what the effective components are. Treatment models need to be adjusted to different subgroups of patients. Finally, we have no data to answer the question as to what are the best treatments among effective treatments such as between psychological versus pharmacological; this is a question that can be clarified only in comparison trials.

Conclusions

Depression is a common condition in diabetes and is associated with multiple adverse economic, social, psychological and biomedical outcomes. The underlying mechanisms to explain the depression–diabetes link appears to be more complicated than previously thought and may involve aetiological processes that explain both conditions and provide new targets for the treatment of both. In the meantime, depression can be treated with antidepressants, psychotherapy, or a flexible combination of both with relatively good results that are comparable to those for patients who have depression but not diabetes. Up to now, no single treatment has been clearly identified that consistently leads to better medical outcomes in patients with both depression and diabetes.

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