Maternal pregabalin exposure linked to major birth defect risk

 

In continuation of my update on Pregabalin 

First trimester exposure to pregabalin may be associated with an increased risk of major birth defects (MBDs), an observational study suggests.

The data from eight Teratology Information Services in seven countries on 164 exposed pregnancies showed that the risk of MBDs was increased a significant threefold compared with 656 unexposed pregnancies.

After limiting the findings to just first trimester exposure and excluding chromosomal aberration syndromes, the rate of major congenitalmal formations was 6.0% among 116 infants exposed to pregabalin as neonates versus 2.1% among 580 unexposed infants. These included four chromosomal and eight structural anomalies affecting the central nervous system (CNS), or the skeletal, cardiac, and skin or vascular systems.

"Our results raise a signal for a possible increase in the rate of MBD after pregabalin treatment during the first trimester of pregnancy", say researcher Ursula Winterfield (Centre Hospitalier Universitaire
Vaudois, Lausanne, Switzerland) and colleagues.

The rate of CNS malformations alone was also significantly higher following pregabalin exposure, increased sixfold, at 3.2% compared with  0.5%.

The researchers note that in all four cases of CNS malformations, the mother had been concurrently taking other substances during pregnancy  in addition to pregabalin and genetic causes have not been ruled out,  but they add: "[G]iven that pregabalin is a centrally acting agent, the possibility that these findings may signal a teratogenic effect in humans needs to be considered."

Other secondary outcomes included rates of live births, spontaneous abortions, preterm deliveries and delivery gestational age and birth weight. Of these, only the rate of live births was lower in the pregabalin-exposed group and this was primarily due to a higher rate of elective and medically indicated pregnancy terminations, suggestive of unplanned pregnancies.

Women were mainly taking pregabalin to treat neuropathic pain, but other indications included psychiatric disorders, epilepsy and restless leg syndrome.

The average daily dose of pregabalin was 150 mg; 77% of women started treatment before becoming pregnant and discontinued at a median  gestational age of 6 weeks. However, more than half of the patients continued treatment beyond this point and 33% beyond 7 weeks. First trimester pregabalin exposure occurred in 96% of patients.

Winterfield and colleagues acknowledge in Neurology that the small sample size and differences across groups in maternal conditions and exposure to concomitant medication mean definitive conclusions cannot be drawn from their findings.

But despite these limitations, Page Pennell (Harvard Medical School, Boston, Massachusetts, USA) and Kimford Meador (Stanford University School of Medicine, Palo Alto, California, USA) say in a related editorial that "this study reflects the prescribing pattern for pregabalin".

They recommend: "Each woman receiving a prescription for a neuropsychiatric indication should receive counselling about the potential risk-benefit ratio for her individually, effective birth control until pregnancy is desired, and increased monitoring during pregnancy and for her child through early neurodevelopment."

Ref : http://www.neurology.org/content/early/2016/05/18/WNL.0000000000002780

FDA-approved drug pregabalin effectively treats RLS symptoms with less side effects

In continuation of my update on pregabalin

A report in the Feb. 13 New England Journal of Medicine confirms previous studies suggesting that long-term treatment with the type of drugs commonly prescribed to treat restless leg syndrome (RLS) can cause a serious worsening of the condition in some patients. The year-long study from a multi-institutional research team found that pregabalin - which is FDA-approved to treat nerve pain, seizures, and other conditions - was effective in reducing RLS symptoms and was much less likely to cause symptom worsening than pramipexole, one of several drugs that activate the dopamine neurotransmission system and are FDA approved for treatment of RLS.

"Our key finding is that dopaminergic drugs, while very effective for many people with RLS, can worsen symptoms in some patients over time, while non-dopaminergic pregabalin is not associated with this disturbing side effect," says John Winkelman, MD, PhD, of the Massachusetts General Hospital Department of Psychiatry, senior author of the study. "Those treating RLS patients with dopaminergic drugs need to be aware of this common complication and exercise caution if their symptoms worsen."

FDA-approved drug pregabalin effectively treats RLS symptoms with less side effects