Lyrica can cause psychosis

Epilepsy: Pregabalin enriches therapy

The most important treatment goal of anti-epileptic pharmacotherapy is to improve the individual's quality of life. The development of modern anti-epileptic drugs has made a decisive contribution to this, because the new drugs primarily brought tolerance advantages over the old anti-epileptic drugs - e.g. B. fewer psychiatric side effects, lower risk of osteoporosis, fewer changes in weight, lower impact on potency and weight, also significantly fewer interactions and lower teratogenicity. Nevertheless, even after therapy with newer substances, many patients still suffer from disruptive effects that impair their performance in everyday life. In addition, seizure control is still inadequate in approximately 30% of patients.

Influence on neurotransmitters

For a new anti-epileptic drug to actually bring about an improvement in the therapeutic spectrum, it must have an advantage in terms of effectiveness, safety, tolerability or pharmacokinetics. Against this background, the newly developed substance pregabalin appears to be a promising candidate for an enrichment in therapy.

Pregabalin is structurally related to gabapentin; both substances are analogues of gamma-aminobutyric acid (GABA), but without GABA-ergic activity. Pregabalin binds with high potency to α2-δ - an auxiliary protein of the voltage-dependent calcium channels. This reduces the calcium influx at the nerve endings and reduces the release of excitatory neurotransmitters such as glutamate, norepinephrine and substance P.

Special pharmacokinetics

Pregabalin has anticonvulsant, analgesic and anxiolytic properties. Pregabalin differs from other anti-epileptic drugs in its simple and predictable pharmacokinetic profile. The substance is absorbed quickly and linearly, only minimally metabolized, not bound to proteins in the plasma and 98% excreted unchanged in the urine. Therefore, no pharmacokinetic interactions - not even with other anti-epileptic drugs, contraceptives or alcohol - are to be expected. The data available so far from clinical studies confirm this assumption.

Endurance test for effectiveness

Pregabalin is intended as an add-on anti-epileptic drug for the treatment of adults with partial seizures with or without secondary generalization. In studies, its effectiveness and tolerability as an additional drug were examined in patients who were not seizure-free despite taking one or more other anti-epileptic drugs. In this difficult-to-treat patient group, pregabalin was 8% (medium dose range) to 19% (maximum dose) freedom from seizures. The responder rates (at least 50% reduction in seizures) were also favorable compared to those of other anti-epileptic drugs. At a medium dose (300 mg), they amounted to approx. 40% and were overall dose-dependent. The rapid onset of seizure reduction is an advantage for clinical practice (onset of action within a week).

The main adverse drug reactions of pregabalin were central nervous events such as drowsiness and dizziness, but mostly only mild to moderate. Serious side effects occurred in only 3.8%. The rate of discontinuation of therapy was comparable to that for placebo.

Take comorbidities seriously

Epilepsy patients suffer from comorbidities significantly more frequently than the general population. For example, depression occurs 5 to 15 times as often - depending on the study used - and accompanying psychoses are 4 to 10 times more common. The anti-epileptic therapy should therefore not exacerbate these additional chronic diseases. Against this background, pregabalin could prove to be advantageous because, on the one hand, it itself has anxiolytic properties and, on the other hand, apparently only rarely leads to cognitive impairment. Braking reaction time and short-term memory were not affected by the anti-epileptic drug in a study on healthy people.

On the other hand, pregabalin (450 mg / d) was found to be significantly positive for sleep quality in a study with volunteers. This could be an important plus point for epilepsy therapy, because epilepsy patients often suffer from sleep disorders: nocturnal seizures can lead to the disruption of the physiological sleep pattern. In addition, some anti-epileptic drugs also impair the structure of sleep. However, sleep deprivation in turn can trigger the occurrence of seizures.