There are more complicated interactions between contraceptives and mood stabilizer medications, many of which are also used for epilepsy. Contraceptive medications can be affected by certain psychotropic medications. Carbamazepine, oxcarbazepine, and topiramate (mood stabilizers which induce the P450 3A4 pathway) can increase the metabolism of oral contraceptives (many of which are substrates of the P450 3A4 pathway), thereby reducing their effectiveness. This effect is also seen with vaginal contraceptive rings, because the hormones contained in these preparations are also metabolized by the liver. In these situations, the patient should either change her contraceptive method or change her mood stabilizer.

Contraceptive alternatives include the birth control patch (which largely avoids liver metabolism) and barrier methods. Mood stabilizers like valproate and lamotrigine do not affect oral contraceptives, but lamotrigine clearance is increased with oral contraceptives that contain estrogen, thereby reducing the effectiveness of the medication. In patients who are taking a traditional mood stabilizer, including Lithium, highly effective contraception is important because these medications can have serious teratogenic effects if a patient accidently becomes pregnant. One option is a high-dose oral contraceptive, but because of the complexity of oral contraceptives and some traditional mood stabilizers as well as side effects of high-dose estrogen, it is important to consider non-hormonal approaches as a primary or adjunctive contraception. St. John’s Wort (an herbal supplement that many patients take for mild depression) can induce the P450 3A4 pathway, thereby inducing the metabolism of oral contraceptives, making them less effective.

There is some concern that progesterone-only pills and high-dose estrogen pills can lead to or worsen depression, although this has not been studied in a controlled fashion that clearly defines depression and addresses the confounding factor of natural fluctuations in mood symptom during various parts of the menstrual cycle. These hormones can increase the metabolism of serotonin in the brain, thereby lowering serotonin levels, which can contribute to depression. It is thought that low-dosed combined oral contraceptives have little risk for causing or worsening depression. However it is important to assess for changes in mood after a patient first starts contraception.

Here is a chart to summarize the interactions between BCP and psychotropic medications:

The data reported in the reference article address an extensive patient pool across all ages.  The data reported comes from reported adverse drug reactions to these medications accumulated over the past 50 years based on reports from practitioners.   The patient base thus includes many patients who may also have been receiving other psychotropic medications and who may have had multiple other medical conditions.

The report findings indicate that movement disorder side effects potentially attributable to antidepressant medications are reported in just under 3% of total side effect reports in the exceptionally large database used collected over a very extended period of time.

Notwithstanding the study’s limitations, the findings do support other reports of individuals on antidepressant monotherapies who have developed movement disorder side effects and there is thus clear indication that, though rare, it is appropriate for prescribers to monitor patients receiving antidepressant medications for a variety of movement disorder side effects, including the following nine subtypes, in order of frequency: tremor, dystonia, parkinsonism, restless legs syndrome, tardive dyskinesia, akathisia, myoclonus bruxism and tics.

The analysis indicates that females were just over twice as likely as men to report movement disorder side effects and that increased age of the patient was also a significant factor leading to increased reporting.  Although there was some variance across antidepressant drug classes (tricyclic antidepressant, serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors and monoamine oxidase inhibitors), all classes of antidepressants appear to carry some limited risk for causing movement disorder side effects.

Not to be lost in this discussion, of course, is that both the more frequently occurring non-movement disorder classified side effects such as digestive disorders, sexual dysfunction, and fatigue/sleepiness and the other lower frequency ones such as hyponatremia, hepatitis, hair loss, and bleeding require monitoring as part of medication oversight activities.

The bottom line for prescribers is to remain vigilant for unwanted complications of treatment with both antidepressants (and all other psychotropic medications) through observation of the patient and inquiry of them about any new symptoms arising during psychopharmacologic treatment.

REFERENCE:    Antidepressants and movement disorders: a post marketing study in the world pharmacovigilance database; Revet, Montastruc, Roussin, et al in BMC Psychiatry; June 16, 2020