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Antidepressants at Normal Doses Linked to First-Time Seizures

Antidepressants, including selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs), have been linked to an increased risk for first- time seizures in patients being treated for depression, new research shows.

Daniel M Keller, Phd, Medscape, Apr 6, 2015

Results of a study conducted by investigators at the University of Basel, in Switzerland, showed that with the exception of tricyclic antidepressants (TCAs) "antidepressant use in depressed patients was associated with an increased risk of seizures compared to non-use. Risk estimates differed across antidepressants and depended on timing of therapy, dose, and sex," the investigators, led by Marlene Blöchliger, a PhD candidate in the pharmacoepidemiology unit at the University of Basel, write.

The findings were presented here at the European Psychiatric Association (EPA) 23rd Congress.


According to the researchers, overdoses of antidepressants are known to induce seizures. However, the investigators wanted to examine whether therapeutic dose ranges were associated with the development of first seizures in patients being treated for depression.

The investigators conducted a retrospective follow-up study with a nested case-control analysis using data from the UK-based Clinical Practice Research Datalink, which includes 8.7 million patients from general practices, beginning in the 1980s.

The data include demographics, patient characteristics, lifestyle variables, medical diagnoses, drug prescriptions, hospital referrals, and laboratory values. The assessment period of her study spanned the years 1998 to 2012.

Of the 151,005 patients diagnosed with depression during that time, 619 had a first seizure.

Dr Völlm attributed the finding to a dose effect in that the study looked at people receiving TCAs within the therapeutic dose range, but possibly at low doses within the range. She suggested that the researchers look at higher therapeutic doses.

But she also noted that newer drugs such as SSRI's "that are marketed as being something very, very safe ― in the end, when you look at it more closely, they are not that safe," causing seizures at a rate higher than TCAs.

These drugs are also associated with other adverse effects, including gastric bleeding and other problems. "Therefore, I think it's very important to do these studies and challenge some of the assumptions we have about what is safe and what isn't," Dr Völlm said.

She commended the use of long-term data in a real-world setting and said that routinely collected data can be valuable for research purposes without commercial funding.

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