The Association Between Diabetes, Metabolic Syndrome and the Use of Antipsychotics Medications

Faded photo of a large abdomen with measuring tape around and a graphic of prescription drugs and insulin injection and glucose monitor to represent the blog topic of Antipsychotic Medication, Metabolic Syndrome, and Diabetes

The use of any medication always has the potential to cause side effects. As the old saying goes “any medication that can affect has a side effect”. That’s true with anyone who is taking antipsychotics. Although antipsychotics can have a host of side effects, this article delves into the use of antipsychotics and the association between type 2 diabetes and metabolic syndrome.

Antipsychotics work in the brain on certain neurotransmitters that affect how a person feels, acts, and responds. Neurotransmitters are essential for transmitting nerve impulses, regulating bodily functions including mood, sleep, movement, and cognition.

As per the NLM (National Library of Medicine) “The prevalence of diabetes is 2-3 fold higher in people with severe mental health issues than the general population. There are concerns that antipsychotics increase the risk of diabetes”. Although there is an increased risk of type 2 diabetes and/or metabolic syndrome in people with first-episode psychosis, the prevalence increases rapidly after the introduction of antipsychotics. While not all antipsychotics work the same way in the body, it is important to have knowledge of which ones pose the higher risk.

Photo of a form on Diabetes, stethoscope, insulin syringe, glucometer, medication, and a chart graphic depicting an increased rate

First Generation/Typical Antipsychotics

First generation or typical antipsychotics block the way the brain uses several neurotransmitters, especially dopamine. They can also block others. First generation antipsychotics are associated with significant extrapyramidal side effects as well as neuroleptic malignant syndrome. First generation may cause weight gain and some aspects of metabolic syndrome, but do not have the highest risk of getting type 2 diabetes.

Chlorpromazine: The brand name of this medication (Thorazine®) isn’t available in the U.S., but generic versions are.
Fluphenazine: The brand names of this medication (Prolixin®, Permitil®) aren’t available in the U.S., but generic versions are.
Haloperidol (Haldol®)
Loxapine (Adusuve®)
Molindone: The brand name of this medication (Moban®) isn’t available in the U.S., but generic versions are.
Perphenazine: The brand name of this medication (Trilafon®) isn’t available in the U.S., but generic versions are.
Pimozide (Orap®)
Prochlorperazine (Compro®)
Thiothixene: The brand name of this medication (Navane®) isn’t available in the U.S., but generic versions are.
Thoridazine: The brand name of this medication (Mellaril®) isn’t available in the U.S., but generic versions are.
Trifluoperazine: The brand name of this medication (Stelazine®) isn’t available in the U.S., but generic versions are.

Second Generation/Atypical Antipsychotics

Second Generation or Atypical antipsychotics block receptors like serotonin and dopamine. Second generation antipsychotics typically cause weight gain. This weight gain is often significant enough to lead to obesity, higher low-density lipoprotein (LDL) cholesterol (the “bad” cholesterol, and an increase in triglycerides (lipids/fats found in the blood).

Aripiprazole (Abilify®, Aristada®)
Asenapine (Secuado®, Saphris®)
Brexpiprazole (Rexulti®)
Cariprazine (Vraylar®)
Clozapine (Clozaril®, Versacloz®)
Iloperidone (Fanapt®)
Lumateperone (Caplyta®)
Lurasidone (Latuda®)
Olanzapine (Zyprexa®, Lybalvi®, Symbyax®)
Quetiapine (Seroquel®)
Paliperidone (Invega®)
Pimavanserin (Nuplazid®)
Risperidone (Perseris®, Risperdal®)

So, why are people taking antipsychotics at higher risk for type 2 diabetes?

“One of the most important findings is that antipsychotics block the ability of the brain to sense sugar and respond by adjusting sugar metabolism in the rest of the body. This may be one mechanism through which antipsychotics cause high blood sugar and diabetes”. (1)

In addition, antipsychotics medications, particularly second generation, are associated with an increased risk of metabolic syndrome, which includes weight gain, glucose dysregulation, and dyslipidemia.

Metabolic Syndrome

What is the criteria for metabolic syndrome? A person meets the criteria for metabolic syndrome if they have at least three of the following:

Excess abdominal weight: A waist circumference of more than 40 inches in males and 35 inches in females
Hypertriglyceridemia: Triglyceride levels that are 150 milligrams per deciliter of blood (mg/dL) or greater.
Low levels of HDL cholesterol: HDL cholesterol of less than 40 mg/dL in males or less than 50 mg/dL in females.
Elevated blood sugar levels: Fasting blood sugar level of 100 mg/dL or greater. If it’s 100 to 125 mg/dL, you have prediabetes. If it’s over 125 mg/dL, you likely have Type 2 diabetes.
High blood pressure: Blood pressure values of systolic 130 mmHg or higher (the top number) and/or diastolic 85 mmHg or higher (the bottom number).

For screening and intervention, it is important for a baseline assessment of weight, blood glucose/A1c and lipid profile when initiating or changing antipsychotic medications with continued monitoring through the span of usage.

In summary it is important to implement measures to prevent diabetes, to screen for diabetes to ensure prompt diagnosis, and to provide effective care. Be aware of the side effects for Typical and Atypical antipsychotic medications. Understand which pose a higher risk and talk to your doctor about what is right for you. Although antipsychotics medications can increase the risk of metabolic syndrome, lifestyle changes can prevent and reverse. Talk to your doctor about what is right for you.

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