Some drug combinations may be more effective than others for schizophrenic patients

  Patients with schizophrenia are often treated with more than one type of psychiatric medication, but a new study suggests that some combinations may be more effective than others.

The findings were published in JAMA Psychiatry.

Antipsychotic drugs are usually the first line of treatment for individuals with schizophrenia. But because these drugs often fail to control symptoms adequately on their own, doctors often prescribe additional psychiatric medications, such as another antipsychotic, an antidepressant, a benzodiazepine, or a mood stabilizer.

"Antipsychotic medications are used to treat psychotic symptoms such as delusions and hallucinations but there is little guidance on what to do for other types of symptoms like depression, anxiety or excitement. Additional medications are often prescribed, but we know little about how different psychiatric drug combinations affect people with schizophrenia," says T. Scott Stroup, MD, MPH, professor of psychiatry at Columbia University Vagelos College of Physicians and Surgeons and lead author of the paper. "Until now we have known virtually nothing about how these strategies compare to each other."

To find out, the researchers conducted a comparative effectiveness study using Medicaid records of 81,921 adults with schizophrenia who had been taking only an antipsychotic drug for at least 3 months before starting either an antidepressant, benzodiazepine, mood stabilizer, or another antipsychotic drug.

The researchers found that individuals with schizophrenia who added an antidepressant were less likely to land in the emergency room or hospital for a mental health issue than those who started another antipsychotic or a benzodiazepine. Antidepressants reduced the risk of hospitalization by 16% compared to antipsychotics and by 22% compared to benzodiazepines. For emergency room visits, antidepressants reduced the risk by 8% compared to antipsychotics and by 18% compared to benzodiazepines.

"Our study adds more evidence that benzodiazepine use should be limited and that combining antidepressants with antipsychotic drugs for individuals with schizophrenia may have benefits," says Stroup. "We still need to know more about when to use antidepressants, which may be useful for conditions other than depression."

Combining medications is often referred to as polypharmacy. "The results of our study should promote rational polypharmacy," added Stroup. He thinks that clinicians will find the results believable and hopes that they will lead to practice changes and improved patient outcomes.

The study is titled, "Comparative Effectiveness of Adjunctive Psychotropic Medications in Patients with Schizophrenia."

https://www.cuimc.columbia.edu/

Some drug combinations may be more effective than others for schizophrenic patients

Apixaban effective in polypharmacy setting

In continuation of my update on Apixaban

The superiority of apixaban over warfarin in patients with atrial fibrillation is maintained in those taking multiple medications, shows further analysis of the ARISTOTLE trial.

 Apixaban

The researchers found superior efficacy of apixaban against the primary thromboembolic endpoint (stroke or systemic embolism) regardless of the number of drugs patients were taking.

By contrast, the advantage of apixaban over warfarin in terms of major bleeding tended to decline in line with the number of drugs patients were taking. The absolute rate reduction per 100 patient-years with apixaban versus warfarin was 1.28 for patients taking up to five medications, falling to 0.82 and 0.66 for those taking six to eight and more than nine drugs, respectively.

"Importantly, the risk reduction of intracranial bleeding did not diminish with an increasing number of concomitant drugs", write the researchers in The BMJ.

"Therefore, the fact that the relative benefit of apixaban over warfarin appears to diminish across groups is due to other types of major bleeding."

They give the example of major gastrointestinal bleeding, which was significantly reduced with apixaban versus warfarin in patients taking up to five drugs, but not in those taking nine or more drugs.

Polypharmacy was common among the 18,201 ARISTOTLE participants, with 76.5% taking at least five concomitant drugs. Patients' average age rose in line with the number of drugs used, as did their stroke and bleeding risk. Patients taking more drugs also had more cardiovascular comorbidities, and also more neurological, renal, endocrine, musculoskeletal, pulmonary, gastrointestinal and haematological comorbidities.

Rates of the primary thromboembolic and bleeding endpoints rose with the number of drugs taken for patients in the apixaban group as well as those in the warfarin group.

Jeroen Jaspers Focks (Radboud University Nijmegen Medical Centre, the Netherlands) and study co-authors stress that "this increased risk of adverse outcomes should be placed in the context of the association between the number of drug treatments and comorbidities present at baseline, indicating a more frail status of patients with polypharmacy."

The researchers suggest that adjusting for these differences would abolish the relationship between the number of drugs used and safety outcomes, but add that the purpose of the study was to use polypharmacy as a marker of patient frailty.

Moreover, increasing frailty did not significantly influence the efficacy of apixaban against stroke or systemic embolism, with the relative risk versus warfarin being 14% among those taking up to five drugs and 24% in those taking more.