Turkish Journal of Endocrinology and Metabolism, (2002) 3 : 95-100 REVIEW

Diabetes and Depression

Haluk Sarg›n Ifl›k Çak›n Mehmet Sarg›n

Dr. Lütfi K›rdar Kartal Training and Research Hospital, Endocrinology and Metabolic Diseases Unit of I. Internal Medicine
Department, ‹stanbul, Turkey

Approximately 30% of patients with diabetes experience comorbid depression. There

is a significant association between depression and hyperglycemia in type 1 and
type 2 diabetes. Also, the adverse consequences of depression in diabetics are the
increased risk of the macro- and microvascular complications of diabetes. On the
other hand, results from the studies suggest that effective management of
depression improves glycemic control. Many newly diagnosed diabetics go through
the typical stages of mourning. These are denial, anger, depression and acceptance.
They may also show rebellion, anxiety, pathological dependency and regression.
Often, individuals with depression do not realize that they are depressed. It is easy to
attribute the symptoms of depression to the diabetes. On the basis of Beck
Depression Inventory scores, cognitive symptoms are the most reliable means to
separate diabetic depressed from diabetic non-depressed patients. In the diagnosis
of depression; one should look for affective and cognitive symptoms, rather than the
somatic-vegetative signs. Panic attacks may resemble hypoglycemic episodes and
vice-versa. Physicians generally select among TCAs, SSRIs, and other newer
antidepressant agents to treat depression, reserving monoamine oxidase inhibitors
and electroconvulsive therapy largely for severe, unresponsive cases. Factors
affecting the selection of an antidepressant for patients with diabetes include
presenting symptoms, coexisting medical conditions, drug interactions and side-
effect profiles.

Key words: Depression, diabetes

Diabetes mellitus is one of the most common prevalence, that is, the percentage of patients with
chronic diseases. Diabetes throws many hormones diabetes who, at some point in their lifetime, will
and brain chemicals out of balance, and these changes have an episode of major depression-appears to be
may open a door to depression (1). Physical about 33% (4,5).
disease destabilizes one’s homeostatic balance and
causes emotional reaction. Every physical disease In the Epidemiologic Catchment Area Program
is a crisis. Illness provokes reactions like anxiety, survey conducted by researchers at Johns Hopkins
guilt, feelings of loss and hopelessness (2). Among University in Baltimore, Maryland; 3.481 community-
patients with type 1 diabetes at the Joslin Diabetes dwelling adults were interviewed at baseline, and a
Center in Boston, the prevalence of depression is 13-year follow-up was completed in 1.897 of these
probably about 30% to 40% (3). The lifetime participants. This study showed that patients with a
major depressive disorder had more than twice the
risk of developing type 2 diabetes compared with
patients without depression (6).
Correspondence address:

Haluk Sarg›n The mean age of onset of depression in diabetes is

Dr. Lütfi K›rdar Kartal Training and Research Hospital, 22 years in type 1 diabetics (3). The age of onset of
Endocrinology and Metabolic Diseases Unit of I. Internal depression in the general population in the United
Medicine Department, ‹stanbul, Turkey States is 27-35 years (7). Depression precedes
E-mail: haluksargin@hotmail.com
Telephone: +90 216 441 39 00/1173 diabetic symptoms in type 2 diabetes, but the
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reverse is true for type 1 (8). It has been found that phenomenon resulting from interactions between
there is a direct correlation between severity of biologic and psychosocial factors. This interaction
depressive symptoms, incidence of complaints of may increase the probability of developing type 2
diabetes, and level of blood glucose in patients diabetes in otherwise healthy individuals.
with type 1 diabetes (9). Diabetics with major depression have a very high
Approximately 30% of patients with diabetes (types 1 rate of recurrent depressive episodes within the
and 2) experience comorbid depression (10). There following five years (23).
is a significant association between depression and A depressed person may not have the energy or
hyperglycemia in type 1 and type 2 diabetes (11). motivation to maintain good diabetic management.
The likelihood of depression is nearly doubled in Depression is frequently associated with unhealthy
patients with diabetes (6). According to a research appetite changes. The suicidal diabetic adolescent
by Ryan Anderson et al, diabetes doubles the odds has constant access to potentially lethal doses of
of depression (12). insulin (14).
Interestingly diabetic schizophrenic or manic One study found that children judged to have a
depressive patients’ glucose regulation does not "Type A" personality structure had an increased
seem to be affected by their psychiatric situation blood sugar elevation in response to stress. Children
(13). Although women are twice as likely as men with a calmer disposition had a smaller glucose
to experience depression, men suffer because they rise when stressed (24). A 1997 study suggested
are less likely than women to seek help. For men, that type 1 patients with a history of a psychiatric
it’s often masked by alcohol or drug abuse, which illness might be at increased risk for developing
may seem more socially acceptable than seeking diabetic retinopathy. Those patients with a psychiatric
psychiatric help. In a study, men were more likely to history were found to have a higher average HbA1c
report moderate to severe depression symptoms and (25). Children whose relatives made more critical
women more moderate to severe anxiety symptoms comments had significantly poorer glucose control.
(14). There was a significant link between depressions Interestingly enough, emotional over involvement
and poor glycaemic control, as measured by the between family members was not correlated with
HbA1c, in men but not in women. One in every poor diabetic control (26). Diabetic adolescents
five people with type 1 or 2 diabetes was depressed had a higher incidence of suicidal ideation than
before they got diabetes (15). expected. Not living in a two-parent home was
associated with poorer long-term diabetes control
The adverse consequences of depression in diabetics
(27). In a study from the University of California,
are the increased risk of the macro- and micro- Los Angeles, patients with higher scores on the
vascular complications of diabetes (16,17). Results Beck Depression Inventory (BDI) were more likely
from the studies suggest that effective management to experience complications of diabetes (28).
of depression improves glycemic control (1,18-20).
In psychosomatic medicine, it had been researched
Clinically significant anxiety is also known to have for long years whether there was a diabetes-specified
an adverse impact on glycemic control in diabetics personality type. Dunlar and Alexander searched
(21). Organic brain syndrome, is the second most for subconscious disagreements specific to diabetics
frequent psychiatric problem in diabetic patients (2). and found out oral characteristics. But it is contro-
According to one study, the initial onset of major versial whether these characteristics are premorbid
or secondary to disease. These people experience
depressive disorder (MDD) seems to be independent
of the onset of type 2 diabetes, but results remain decreasement in energy levels, chronic fatigue,
irritability, depression and delay in psychosexual
equivocal for type 1 diabetes (22). However, in both
maturation (2).
type 1 and type 2 diabetes, diabetes-related psycho-
logical and physiological processes may be involved Recent studies have suggested that effective treatment
in the higher recurrence and longer duration of of depression can improve diabetic control. In a
MDD and depressive symptomatology. MDD in study by Lustman and colleagues, glucose levels
diabetic individuals represents a multidetermined were shown to improve as depression lifted (18).

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Depressive symptom severity is associated with • Difficulty sleeping or significantly increased

poorer diet and medication regimen adherence, need to sleep
functional impairment, and higher health care costs • Weight loss or weight gain.
in primary care diabetic patients (29-31). Based on • Feelings of guilt or worthlessness
findings of an increased prevalence of diabetes among
• Low energy level
those with a major depressive disorder, "depression
may have an impact biologically" that affects insulin • Difficulty making decisions or concentrating
usage (6). • Suicidal thoughts
• Feeling agitated or sluggish nearly every day
In a 10-year prospective trial of 24 children with
insulin-dependent diabetes mellitus, three factors Selection of antidepressant agents
were independently associated with the risk of
retinopathy: duration of diabetes, duration of time Physicians generally select among TCAs, SSRIs,
with poor glycemic control and duration of time with and other newer antidepressant agents to treat
symptoms of major depression (34). depression, reserving monoamine oxidase inhibitors
and electro convulsive therapy largely for severe,
There was a threefold increase in incidence of unresponsive cases (38). Factors affecting the
coronary disease in the diabetic patients with selection of an antidepressant for patients with
depression versus in those without depression (32). diabetes include presenting symptoms, coexisting
There has been some speculation, that serotonin medical conditions, drug interactions (patients
dysfunction may be a factor in both depression and with diabetes typically take many medications),
lack of glycemic control. Preliminary evidence has and side-effect profiles (38,39). The older tricyclic
shown that serotonin may increase response to antidepressants can increase glucose levels in non-
insulin (33). depressed diabetics (14).
TCAs have the potential for hyperglycemia,
Making the diagnosis
weight gain and orthostatic hypertension and other
On the basis of Beck Depression Inventory scores, cardiovascular side effects. Drug interactions with
cognitive symptoms are the most reliable means to other medications are another problem with TCAs
separate diabetic depressed from diabetic non- (38). TCAs are well-known to lead to "sweets"
depressed patients (35,36). In the diagnosis of cravings and weight gain (40,41). Also their effect
depression; one should look for affective and to impair memory, worsens the patient’s cooperation
cognitive symptoms, rather than the somatic- with the glycemic control instructions (40).
vegetative signs (2). Panic attacks may resemble
Since 1964, MAOIs are known to suddenly reduce
hypoglycemic episodes and vice-versa (14).
plasma glucose to the degree of requiring emergency
Many newly diagnosed diabetics go through the intravenous glucose (42), and so are not a good
typical stages of mourning. These are denial, anger, choice for the diabetic patient.
depression and acceptance (14). They may also
In the studies of antidepressants in diabetics,
show rebellion, anxiety, pathological dependency
nortriptyline and fluoxetine effectively treated
and regression (2). Often, individuals with depression
depression (1,18). There have been four studies on
do not realize that they are depressed. It is easy to the use of fluoxetine in NIDDM patients (43-46).
attribute the symptoms of depression to the diabetes.
Treatment with fluoxetine also improved glycemic
Symptoms of depression control and reduced severity of depression (1,46).
The combination of cognitive–behavioral therapy
These are based on the Diagnostic and Statistical (CBT) and supportive diabetes education proved to
Manual of the American Psychiatric Association, be effective in treating depression in patients with
4 th Edition. (DSM-4) (37). A clinician would diabetes, and improved glycemic control (20). The
diagnose depression if a patient had five or more antianxiety agent alprazolam was also found to
of the following symptoms for at least two weeks: improve glucose regulation (47).
• Depressed mood for most of the day Treatment of depression with selective serotonin
• Decreased pleasure in normal activities reuptake inhibitors (SSRIs) and other newer classes

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of antidepressants has not been associated with positive ways of thinking. Cognitive therapy can
hyperglycemia in persons without diabetes (41). also be helpful in non-depressed individuals who
Although weight gain and sedation are not are having trouble with their diabetic management.
generally caused by the SSRIs and other newer
antidepressants, some of them cause agitation, The importance of follow-up
gastrointestinal distress, and sexual dysfunction. Residual symptoms of depression after treatment
SSRIs are easier to administer and have fewer side predict recurrence (49). In general; it’is important
effects, so they are more often used as the first line that the patients be almost asymptomatic. The presence
antidepressants. Decreased sexual desire may be a of diabetes complications and hyperglycemia predicts
sensitive issue for some diabetics, especially those recurrence of depression following successful
who have some sexual difficulty due to their treatment, as well as diminished response to both
diabetes. Often, treatment of the depression can result
psychotherapy and pharmacotherapy (23,49,50).
in much better sexual functioning. Bupropion,
About 60% of patients who are treated with anti-
mirtazapine, and nefazodone do not usually cause
depressants can be expected to achieve a remission
sexual dysfunction. Bupropion is sometimes used
of depression, and approximately the same is true
in combination with an SSRI to alleviate sexual
for psychotherapy (23). Diabetic patients have
dysfunction (i.e., decreased libido, anorgasmia, delayed
about one episode of depression annually and even
ejaculation). Drug interactions with SSRIs are not
after successful treatment, recurrence is really the
common, but this class of antidepressants interferes
with the cytochrome P450 system (principally the norm rather than the exception (51).
2D6 isozyme) and may interfere with the metabolism
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