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Lithium may provide answer to antidepressant shortcomings

S. Nassir Ghaemi

NEW ORLEANS — In a presentation here, S. Nassir Ghaemi, MD, MPH, of Tufts University School of Medicine, discussed shortcomings of antidepressants, as well as the promise of lithium at low doses for suicide prevention in depression.

“There is not much treatment-resistant depression, really,” Ghaemi said. “It’s not that the antidepressants don’t work, it’s that the diagnosis of [major depressive disorder (MDD)] doesn’t work.”

He asserted that 25% of treatment-resistant depression is misdiagnosed bipolar depression and 75% is due to the “invalidity of the concept of MDD.”

In addition, there is strong evidence that antidepressants have a lacking effect on MDD, according to Ghaemi.

Data on antidepressants for MDD

An FDA meta-analysis of all maintenance randomized controlled trials on antidepressants for MDD indicated a mean relapse rate difference of 18% compared with placebo.

Antidepressants resulted in a 52% reduction in relapse vs. placebo, and 94% of relapses occurred after 2 weeks post-randomization.

According to Ghaemi, these findings indicated no real clinical benefit of antidepressants for MDD, as they only worked half of the time and can cause significant side effects.

Further, pharmaceutical studies may be misleading regarding antidepressant efficacy.

“Pharmaceutical industry studies are not so straightforward in terms of showing the drugs clearly work very effectively and work straightforwardly,” he said. “I’m not saying they don’t work at all; I do say that they work for severe depression. But I think there’s a lot of questions about how much benefit we get outside of severe depression.”

More effective treatment options

Ketamine has been recently shown to improve depression and is becoming increasingly popular.

Ghaemi cited research that indicated ketamine takes effect in 2 hours, has a treatment duration of 1 to 2 weeks, and has resulted in 90 deaths in the United Kingdom in 8 years.

Overall, ketamine is an illicit drug that is unsafe, but may be safe at certain dosages, according to Ghaemi.

More maintenance data is needed.

For suicide prevention in depression, Ghaemi strongly endorsed the utility of lithium at low doses.

“Randomized trials are the most definitive evidence,” Ghaemi said. “There’s only one drug that’s been shown in randomized trials to prevent and treat suicide and that’s lithium.”

Selective serotonin reuptake inhibitors have been shown to increase risk for suicide by 90% among young adults and children, while lithium decreases risk by 40%, according to Ghaemi.

“So, why are we not giving lithium to the 18-year-old who is depressed and giving him Prozac instead?” he asked.

Further, research has shown neuroprotective benefits of lithium; however, more research is needed.

Regarding concerns about kidney toxicity associated with lithium, Ghaemi stated that while there is evidence of the association, risk increases as dosage and treatment duration increases. Therefore, low doses of lithium may be a viable option.

“Treatment resistance may reflect the invalidity of the MDD concept because it’s so common,” Ghaemi said. “It’s not about the drugs; it’s about giving the wrong kinds of drugs for the wrong kinds of clinical diagnoses. Antidepressants are clearly ideally effective in two-thirds of patients with so-called MDD... and they worsen mixed states whether it’s in MDD or bipolar.”

Long-term efficacy of antidepressants for prevention of depressive episodes in MDD is not well established in scientific research, he said.

“The best prevention for suicide is lithium, not antidepressants,” he concluded. – by Amanda Oldt

Reference:

Ghaemi SN. Reexamining “depression” and antidepressants: A new approach. Presented at: U.S. Psychiatric and Mental Health Congress; Sept. 16-19, 2017; New Orleans.

Disclosure: Ghaemi reports financial ties with Sunovion Pharmaceuticals.