Common Somatic Meds May Offer Benefits in Psychosis

Commonly prescribed drugs, such as statins and metformin, for physical health problems seemed to lead to better outcomes for patients with serious mental disorders, according to an analysis of Swedish registries.

Of 142,691 patients with bipolar disorder, schizophrenia, or nonaffective psychosis, those exposed to statins (hydroxymethyl glutaryl coenzyme A reductase inhibitors or HMG-CoA RIs), L-type calcium channel (LTCC) antagonists, and biguanides demonstrated reduced rates of psychiatric hospitalization, reported Joseph Hayes, PhD, of the University College London, and colleagues.

Exposure to any of the study drugs was also associated with reductions in self-harm for patients with bipolar disorder and schizophrenia, they wrote in JAMA Psychiatry.

“At this stage, we are not suggesting people with these mental illnesses change their treatment,” Hayes told MedPage Today in an email. “However, there is evidence that people with schizophrenia, bipolar disorder, and other psychotic illnesses tend to have their physical health undertreated.”

John Torous, MD, director of the digital psychiatry division of Beth Israel Deaconess Medical Center in Boston, said that patients with mental health disorders typically have higher rates of the conditions treated by the study drugs, primarily high cholesterol, hypertension, and diabetes. As a result, treating physical health problems in this group of patients could serve to augment mental health outcomes as well, he said.

“People with psychotic illness (bipolar disorder and schizophrenia) have a mortality rate that’s about 20 years earlier than the general population,” Torous, who was not involved with the study, told MedPage Today. “That mortality is due to cardiovascular disease, and if you think about what leads to cardiovascular disease, it’s high cholesterol, high blood pressure, and diabetes — all the things the authors were looking at, drugs that treat these conditions.”

Although he emphasized that the results from this study could not determine causation, Torous speculated that the association could be caused by these physical health drugs aiding the metabolism or absorption of other psychiatric drugs. They could also reduce inflammation, which is associated with more severe illnesses, he said.

The study linked data from the Total Population Register, Migration Register, Cause of Death Register, Prescribed Drug Register, and National Patient Registers in Sweden from January 1, 1973 to December 31, 2016, the authors explained.

Individuals were included if they had a diagnosis of bipolar disorder, schizophrenia, or nonaffective psychosis consistent with the codes from the ICD revisions 9 and 10, and had received a psychotropic medication like antipsychotics, lithium, or mood stabilizers from October 1, 2005 to December 31, 2016. They were considered “exposed” to the drugs examined in this study if they dispensed two prescriptions within 3 months, the authors stated.

In total, 76,759 patients with bipolar disorder, 30,954 with schizophrenia, and 34,978 with nonaffective psychosis were included.

The authors reported that the HMG-CoA RI exposure periods were tied to reduced rates of psychiatric hospitalization (P<0.001 for all) in:

• Bipolar disorder: adjusted hazard ratio 0.86 (95% CI 0.83-0.89)
• Schizophrenia: aHR 0.75 (95% CI 0.71-0.79)
• Nonaffective psychosis: aHR 0.80 (95% CI 0.75-0.85)

They also found reduced self-harm rates with HMG-CoA RI in bipolar disorder (aHR 0.76, 95% CI 0.66-0.86) and schizophrenia (aHR 0.58, 95% CI 0.45-0.74, P<0.001 for both).

Significant reductions in psychiatric hospitalization occurred when patients were administered LTCC antagonists at the following rates after adjusting for age, year, number of previous hospitalizations, psychiatric medication exposure, and number of exposure periods:

• Bipolar disorder: aHR 0.92 (95% CI 0.88-0.96, P<0.001)
• Schizophrenia: aHR 0.80 (95% CI 0.74-0.85, P<0.001)
• Nonaffective psychosis: aHR 0.89 (95% CI 0.83-0.96, P=0.002)

Those with nonaffective psychosis only saw significant reductions for self-harm with LTCC antagonists (aHR 0.56, 95% CI 0.42-0.74, P<0.001), the authors stated.

Finally, during biguanide exposure, psychiatric hospitalization rates were reduced in bipolar disorder (aHR 0.80, 95% CI 0.77-0.84, P<0.001), schizophrenia (aHR 0.73, 95% CI 0.69-0.77, P<0.001), and nonaffective psychosis (aHR 0.85, 95% CI 0.79-0.92, P<0.001), while self-harm was reduced in bipolar disorder (aHR 0.73, 95% CI 0.62-0.84, P<0.001) and in schizophrenia (aHR 0.64, 95% CI 0.48-0.85, P<0.001).

Hayes said that, as with any observational study, it was possible confounding factors associated with severe mental illness influenced these findings. However, the researchers also examined the association between psychiatric conditions and patients taking thiazide diuretics (drugs used to treat blood pressure) and did not find reductions in psychiatric hospitalizations in this population (aHR 0.99, 95% CI 0.93-1.05, P=0.64), he said.

“This goes against the argument that what we observe is just related to a greater period of stability,” Hayes said. “We also examined non-psychiatric hospitalizations and as we would expect with drugs that only modify illness risk in the long term (HMG-CoA RIs and LTCC antagonists), we found no association between this outcome and being on or off the medication.”

The authors acknowledged that due to the nature of the study, the individuals examined were likely less healthy than the general population, and most were at least age 50 at the initial follow-up, so a survival bias may have affected the results. The study was also limited by a lack of data in the registries on the dose or supply of prescriptions, as well as whether patients adhered to treatment.