SSRIs face next-generation antidepresant replacement

WASHINGTON, DC, United States (UPI) — A study released Saturday could pose more bad news for the beleaguered anti-depressant field, but some analysts think the selective serotonin reuptake inhibitors market has run its course anyway and will soon be replaced by triple reuptake inhibitors.

‘Triple reuptake inhibitors will be the next blockbusters in major depression,’ Natalie Taylor, an analyst with Decision Resources, told United Press International. ‘With their mechanism of action, they`re going to offer a clinical difference in efficacy or in tolerability,’ Taylor said. Triple reuptake inhibitors, or TRIs, block the uptake of serotonin, norepinephrine and dopamine. ‘SSRIs will still be considered first-line therapies for a couple of years, but TRIs might have what it takes to replace SSRIs from that spot and then they`re going to start impacting patient share,’ Taylor said.

TRIs include St. John’s Wort

Forest, which makes two SSRIs, declined to comment, and GlaxoSmithKline, which manufactures Paxil, told UPI it could not comment until it had a chance to review the published study. Eli Lilly, manufacturers of Prozac, the most commonly known Single Serotonin Reuptake Inhibitor (SSRI) defended the safety of SSRIs, including its Prozac, on heart function. ‘There is considerable data in the public domain in support of the benefits of SSRIs and cardiac function in patients with depression,’ Lilly spokesman Morry Smulevitz told UPI.

‘While we welcome further research on depression, results from Lilly`s sponsored Prozac clinical trials indicate that therapeutic doses of Prozac do not have a harmful effect on cardiac conduction, heart rate or blood pressure,’ Smulevitz added. Taylor said she doubted the findings would significantly affect the SSRI market. The sector has already taken a big hit from the concern about the link to increased suicide risk. Also, the current findings don`t conclusively point to SSRIs as the culprit, so it`s likely to be too nebulous to have much of an impact on the field.

In addition, generic competition is stealing a lot of market share from the branded medications, Taylor said. Of the six SSRIs on the market, only two are still on patent: Pfizer`s Zoloft and Forest`s Celexa. But these too will soon go off patent. Zol oft`s patent is scheduled to expire in June, and Celexa loses market exclusivity in 2009, she said. In the study, Watkins and colleagues analyzed clinical data of more than 900 patients receiving a cardiac angiography procedure. Approximately 19 percent of the patients were taking an anti-depressant, with 66 percent of those on SSRIs.

Over the course of three years, 21.4 percent of the patients on antidepressants had died compared to 12.5 percent of those not on the medications.Patients on the medications had a 55-percent higher risk of dying even after controlling for age, gender, heart-pumping strength, smoking, heart procedures, other illnesses, severity of depression and education. The difference in death risk between SSRIs and other anti-depressant medications was not statistically significant.

A tripple quadruple reuptake inhibitor, St John’s wort has been shown to inhibit the synaptosomal uptake of serotonin, dopamine and noradrenaline (norepinephrine) with approximately equal affinity. Other in vitro binding assays carried out using St John’s wort extract demonstrated significant affinity for adenosine, GABA(A), GABA(B) and glutamate receptors as well. In vivo St John’s wort extract leads to a downregulation of beta-adrenergic receptors and an upregulation of serotonin 5-HT(2) receptors in the rat frontal cortex and causes changes in neurotransmitter concentrations in brain areas that are implicated in depression. In studies using the rat forced swimming test, an animal model of depression.