A look at diabetes, depression, and the use of antidepressant medications

By Donna Itzstein, Pharmacist and Credentialled Diabetes Educator

Diabetes, depression, and anxiety frequently co‑occur and interact in ways that can significantly affect outcomes. People living with diabetes are almost twice as likely to experience depression compared with the general population, regardless of diabetes type. In turn, depression and anxiety can impair self‑management, worsen glycaemic outcomes, and increase complications and need for healthcare.

For clinicians, recognising these bidirectional relationships, and understanding how pharmacological treatments for both mental health and diabetes influence each other, is central to providing effective, person‑centred care.

Clinical features

Depression in people with diabetes may present with persistent low mood, fatigue, sleep disturbance, appetite change, and cognitive difficulties. Anxiety commonly manifests as excessive worry, hypervigilance, and fear, including fear related to hypoglycaemia or long‑term complications.

Symptoms are often mistakenly attributed to “poor motivation” or “non‑adherence”, when in fact they reflect significant psychological distress.

Prevalence and impact

• Depression and anxiety are more common in people with diabetes than in those without
• Psychological distress is associated with poorer glycaemic control, reduced engagement in self‑care behaviours, and higher rates of hospitalisation
• Diabetes distress (distinct from clinical depression) is also common and should be actively assessed

Validated screening tools routinely used in practice include:

• PHQ‑9 (depression)
• GAD‑7 (anxiety)
• PAID scale (diabetes distress)
• HFS‑II (fear of hypoglycaemia)

Why diabetes and mental health conditions co‑exist

Psychosocial contributors

• Treatment burden: glucose monitoring, medication adjustments, dietary planning and frequent appointments
• Complex regimens: insulin use, carbohydrate counting and risk of hypoglycaemia increase cognitive and emotional load
• Social factors: stigma, reduced spontaneity, and perceived judgement
• Complications: pain, visual impairment, or neuropathy further increase psychological vulnerability

Biological contributors

• Dysregulation of stress hormones
• Inflammatory processes
• Neuroendocrine changes affecting mood and motivation

Importantly, depression itself increases the risk of developing type 2 diabetes through behavioural pathways (reduced activity, unhealthy eating, smoking) and physiological mechanisms (insulin resistance related to chronic stress).

The self‑reinforcing cycle

Depression and anxiety can reduce adherence to diabetes management; worsening glycaemic control can, in turn, intensify psychological symptoms. Without early recognition and integrated treatment, this cycle can become entrenched and difficult to interrupt.

Effective care requires simultaneous attention to metabolic and psychological health. Interventions include:

• Psychological therapies (e.g. CBT, motivational interviewing)
• Lifestyle interventions
• Pharmacotherapy for mental health and/or diabetes
• Multidisciplinary care involving GPs, diabetes educators, dietitians, and mental health professionals

Medication choice deserves particular attention, as treatments for one condition can meaningfully affect the other.

Antipsychotic medications and diabetes risk

Many antipsychotic medications adversely affect metabolic health through:

• Weight gain
• Increased insulin resistance
• Dyslipidaemia
• Elevated blood glucose

Higher‑risk agents (examples)

• Clozapine
• Olanzapine
• Quetiapine
• Risperidone

Lower metabolic risk (relative)

• Aripiprazole
• Brexpiprazole
• Amisulpride

Practical considerations

• Baseline and ongoing monitoring of weight, HbA1c, fasting glucose and lipids is essential
• Metabolic risk should be discussed with patients during shared decision‑making
• Where clinically appropriate, consider agents with a more favourable metabolic profile—particularly in people with pre‑existing diabetes or high cardiometabolic risk

Antidepressant medications and diabetes

Large observational studies suggest a modest association between antidepressant use and new‑onset type 2 diabetes. However, causality remains unclear, and confounding by indication (i.e. depression itself increasing diabetes risk) is likely.

Key points for practice

• Untreated depression carries significant risks and should not be left unmanaged due to concerns about diabetes alone
• SSRIs and SNRIs are commonly used and generally preferred due to tolerability
• Tricyclic antidepressants are more likely to contribute to weight gain and insulin resistance

Practical approach

• Monitor metabolic parameters, particularly with long‑term antidepressant use
• Address lifestyle factors proactively
• Reassure patients that mental health treatment remains a priority

Diabetes medications and mood

Emerging evidence suggests that glucose‑lowering therapies may influence depression and anxiety risk.

Associated with lower risk of depression

• Metformin
• DPP‑4 inhibitors
• GLP‑1 receptor agonists
• SGLT2 inhibitors

Associated with higher risk (context‑dependent)

• Insulin
• Sulfonylureas

This association may reflect:

• Weight gain versus weight neutrality or loss
• Hypoglycaemia risk
• Psychological impact of treatment escalation

Weight and mood

Weight change appears to be an important mediator:

• Weight gain can negatively affect mood and self‑image
• Weight loss or improved metabolic control may improve psychological well‑being

Insulin initiation

• Insulin should not be delayed when clinically indicated.
• Initiation often coincides with emotionally challenging points in the disease trajectory (e.g. new type 1 diagnosis or long‑standing type 2 diabetes), increasing vulnerability to depression or anxiety.
• Additional education, dietetic input and psychological support are often beneficial at this stage.

Barriers to integrated care

• Stigma surrounding mental health
• Fragmented services
• Limited access to psychological care
• Time constraints in routine diabetes reviews

Proactively asking about emotional wellbeing and normalising psychological support can reduce these barriers.

Conclusion

Diabetes and depression are closely linked conditions that require integrated care. Medications used to treat mental health and diabetes can influence both metabolic and psychological outcomes—positively and negatively.

For best outcomes:

• Screen routinely for psychological distress
• Consider mental health implications when prescribing diabetes therapies
• Monitor metabolic effects when prescribing psychotropic medications
• Use shared decision‑making and multidisciplinary support

Treating the whole person, rather than isolated conditions, improves both quality of life and long‑term health outcomes.