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Controversies and Challenges of Treating Mental Illness
San Diego, CA—The controversies and challenges surrounding the treatment of mental illness were addressed during a session at the recent Psych Congress.
In a session on the current state of antidepressant therapy, Michael E. Thase, MD, professor of psychiatry, Perelman School of Medicine, University of Pennsylvania, discussed controversies in the use of antidepressants to treat depression as well as promising new drugs under investigation. Currently, consensus from guidelines continues to recommend generic selective serotonin reuptake inhibitors (SSRIs), sero- tonin-norepinephrine reuptake inhibitors (SNRIs), and the norepinephrine-dopamine reuptake inhibitor (NDRI) bupropion as agents for first-line treatment. However, these agents are limited and there is controversy over their true efficacy, noted Dr Thase. Randomized clinical trials demonstrate the limited efficacy of antidepressants, with benefit reported in only 10% to 20% of patients.
This controversy is amplified by the fact that antidepressant use is on the rise in the US, noted Dr Thase. Currently, 11% to 13% of adults take antidepressants, which has increased from 5.8% to 10.1% of adults taking them between 1996 and 2005. In addition, there has been an increase in use of antidepressants to treat anxiety and adjustment disorders. Moreover, their use is associated with decreased rates of using psychotherapy and counseling as treatment.
Additional limitations include intolerable side effects experienced in about 10% of patients, inconsistent effects on key symptoms of depression such as insomnia and anxiety, and their relatively slow onset of action.
Evolving Drug Treatments for Depression
Thus, alternative therapies are needed. Dr Thase discussed several newer antidepressants (Table 1), second generation antipsychotic medications (SGAs), and ketamine.
Among the current issues emerging from these newer therapies is whether combining antidepressants represents an advancement in clinical practice or is just a current trend. Although it was once considered bad practice to combine antidepressants, Dr Thase said that it is now commonly done for treatment-resistant depression even though no antidepressant is approved to be used in this way. The preferred combination is bupropion and mirtazapine.
Another issue is whether SGAs should be classified as antidepressants in the first place. Additionally, there are questions about their sustained efficacy, cost, and side effects. Dr Thase said that 4 SGAs (aripiprazole, olanzapine, quetiapine, and risperidone) have established efficacy as adjuncts to antidepressants, and 3 (olanzapine, quetiapine, and lurasidone) have established efficacy as monotherapies for biopolar depression. One drug (quetiapine) has established efficacy as monotherapy for major depressive disorder (MDD).
Among the issues raised with the use of SGAs is whether their efficacy is sustained, whether they are cost-effective compared to other options, and their increased risk of tardive dyskinesia and metabolic complications.
Overall, Dr Thase said that it is still unknown whether the recently introduced antidepressants provide a suitable alternative therapy to the current first-line treatments, and offer more rapid onset effect.
The Promise of Ketamine-like Agents
He said the most promising drugs on the horizon are ketamine-like drugs. Ketamine, an NMDA [glutamate N-methly-D-asparate] receptor antagonist, has been shown to have a large and rapid onset of efficacy (within 24 hours and maintained for 7 days after infusion) when used to treat MDD, according to Murrough et al [Am J Psychiatry. 2013;170(10):1134- 1142].
Dr. Thase noted, however, that there are still many unknowns about ketamine for the treatment of depression, including whether tolerance or neurotoxicity will develop with repeated doses.
Christoph U. Correll, MD, professor of psychiatry and molecular medicine, Hofstra North Shore–LIJ School of Medicine, medical director, recognition and prevention program, Zucker Hillside Hospital, talked about the multiple challenges of treating patients with mental illness and metabolic syndrome.
5 Challenges of Managing Mental Illness
He outlined the top 5 challenges that health care professionals need to be aware of when managing a mental illness in a patient, all of which revolve around the strong link between mental disorders and ill effects on physical health, particularly metabolic syndrome and related cardiovascular disease (Table 2).
1. The substantial burden of mental illness on physical health. He cited data from Limm et al showing that mental illness is attributed to risk factors such as high blood pressure, behavior-associated risk factors (tobacco use, poor diet, physical inactivity, drug use), high fasting plasma glucose, high total cholesterol, and high body mass index [Lancet. 2012;380:2224- 2260].
2. The increased risk of metabolic syndrome. Dr Correll said that the link between depression and metabolic syndrome has been established in 61 analyses of over 16,000 patients. Data from Vancampfort et al show an overall rate of metabolic syndrome of 28% in patients with depression, and significantly higher rates of metabolic syndrome compared with age-and gender-matched general population samples [Psychol Med. 2014;44:2017-2028].
He also cited data from the RAISE [Recovery After an Initial Schizophrenia Episode] study that assessed cardiometabolic risk in first-episode schizophrenia patients. Correll et al showed that metabolic syndrome and smoking were more common in these patients compared to similarly aged adults in the general population.
Furthermore, these patients had dyslipidemia and pre-hypertension similar to adults in the general population who were 16 to 20 years of age. In addition, the study found a correlation between higher body composition values and total psychiatric illness duration, with brief antipsychotic treatment duration associated with higher metabolic values [JAMA Psychiatry. 2014;71:1350-1363].
3. The effect of psychotropic agents on metabolic status. Dr Correll emphasized the predictable adverse cardiometabolic effects of medication-induced weight gain, as well as adverse effects on glucose and lipid metabolism that can occur independent of changes in weight gain.
4. The need for cardiometabolic monitoring. Dr Correll cited recommendations from an American Diabetes Association consensus development conference on antipsychotic drugs, obesity, and diabetes. The conference focused on monitoring patients on antipsychotic drugs for the development of significant weight gain, dyslipidemia, and diabetes [Diabetes Care. 2004:27:596-601].
Despite these recommendations, data from Mitchell et al showed that metabolic monitoring of people on antipsychotic medication remains low and most patients still do not receive adequate testing [Psychol Med. 2012;42:125-147].
5. The management of cardiovascular risk factors and morbidity. Of the interventions to reduce cardiovascular risk, smoking cessation had the greatest effect on reducing cardiovascular risk, followed by an active lifestyle, healthy weight, lowering cholesterol, decreasing weight, and lowering blood pressure.
Dr Correll stressed the need to educate and counsel patients on nutrition and exercise, and discussed educational and psychosocial programs that promote the gradual implementation of lifestyle changes around habits related to diet, exercise, and smoking.
If further intervention is needed, he suggested considering switching to a lower-risk antipsychotic and/or using weight loss pharmacologic interventions, or referral to a specialist.
Dr Correll concluded the session by emphasizing the need to proactively manage physical illness in patients with severe mental illness.—Mary Beth Nierengarten
