Abstract
Rocamora R, Ley M, Molins A, Toledo M, Sansa G, Bertol V, Becerra J-L,
Carreño M, Mauri J-Á Epilepsy Behav
2018;79:87–92. Depression is the main psychiatric comorbidity in epilepsy with an
estimated prevalence between 20% and 55% and one of the main
determinants of quality of life. The aim of this study was to
investigate the effect of lacosamide (LCM) on mood and anxiety
symptoms in patients with focal onset seizures (FOS). The secondary
objective was to evaluate if the potential modifications in
variables were related to seizure control or to the intrinsic effect
of LCM. We performed a prospective multicenter study in 8 tertiary epilepsy
centers in adults with FOS in which LCM was initiated as add-on
therapy. Patients’ mood and quality of life were evaluated
through questionnaires and scales such as the Beck Depression
Inventory-II (BDI-II), the State–Trait Anxiety Inventory
(STAI-S/T), the Hospital Anxiety and Depression Scale (HADS), and
the Quality of Life in Epilepsy-10 (QOLIE-10). Initiation of
psychotropic medication was not allowed during the observation
period. Patients with diagnosis of major depression or bipolar
disorder were excluded. Evaluations were scheduled before LCM
treatment, at 3 and 6 months. Forty-nine patients were included (51% female) with an average age of
39.5 years (range 18–65). At the start of treatment with LCM,
65.3% of the patients were on treatment with one antiepileptic drug
(AED). Based on BDI-II, 38.8% of patients had depressive symptoms
and 46.9% according to HADS Depression (HADS-D), 63.3% of patients
presented pathological levels of anxiety (STAI-S/T), and 44.9%
according to HADS Anxiety (HADS-A). Quality of Life in Epilepsy-10
showed that 57.1% of patients had a relevant reduction in their
quality of life. After LCM, the score on the BDI-II depression scale
decreased significantly (p < 0.001). Based on the STAI and
HADS anxiety scales, patients who had a pathological anxiety at
baseline, significantly improved. The QOLIE-10 improved
significantly over the observation period (p < 0.001). At 6
months, 28.3% of patients were seizure-free (67.4% were responders).
The improvements on depression and anxiety scores were not
statistically related to seizure control. Lacosamide seems to have a positive effect on depressive and anxiety
symptoms. Although the efficacy of LCM in seizure control was
demonstrated, the antidepressant and anxiolytic effect on mood and
anxiety seems to be an independent factor.
Guilfoyle SM, Follansbee-Junger K, Smith AW, Combs A, Ollier S, Hater
B, Modi AC Epilepsia 2018;59:146–154. To examine baseline psychological functioning and antiepileptic drug
(AED) behavioral side effects in new onset epilepsy and determine,
by age, whether baseline psychological functioning predicts AED
behavioral side effects 1 month following AED initiation. A retrospective chart review was conducted between July 2011 and
December 2014 that included youths with new onset epilepsy. As part
of routine interdisciplinary care, caregivers completed the Behavior
Assessment System for Children, 2nd Edition: Parent Rating Scale to
report on baseline psychological functioning at the diagnostic visit
and the Pediatric Epilepsy Side Effects Questionnaire to identify
AED behavioral side effects at the 1-month follow-up clinic visit
following AED initiation. Children (age = 2–11 years) and
adolescents (age = 12–18 years) were examined separately. A total of 380 youths with new onset epilepsy (Mage = 8.9
± 4.3 years; 83.4% Caucasian; 34.8% focal epilepsy, 41.1%
generalized epilepsy, 23.7% unclassified epilepsy) were included.
Seventy percent of youths had at-risk or clinically elevated
baseline psychological symptoms. Children had significantly greater
AED behavioral side effects (M = 25.08 ±
26.36) compared to adolescents (M = 12.36 ±
17.73), regardless of AED. Valproic acid demonstrated significantly
greater behavioral side effects compared to all other AEDs, with the
exception of levetiracetam. Higher hyperactivity/impulsivity at
baseline significantly predicted higher AED behavioral side effects
1 month after AED initiation in both age groups. Younger children seem to be more prone to experience behavioral side
effects, and these are likely to be higher if youths with epilepsy
have baseline hyperactivity/impulsivity. Baseline psychological
screening, specifically hyperactivity, can be used as a precision
medicine tool for AED selection.Introduction
Material and Methods
Results
Conclusion
Objective
Methods
Results
Significance
Commentary
Anxiety (12–22%; 1), depression (22–55%; 2) and behavioral changes, like the ones seen in attention deficit with hyperactivity (ADHD; 27%; 3), are common in people with epilepsy. They are considered risk factors and co-existing manifestation of the disease (4). Symptoms of depression and anxiety often precede the onset of seizures and the diagnosis of epilepsy (4, 5); vice versa, the diagnosis of epilepsy is often followed by the development of active psychopathology. The consequence of this constellation of seizures and psychiatric symptoms is often worsening quality of life that requires a comprehensive therapeutic approach.
If we think of the relation between mood, behavior, and epilepsy as a spectrum of a common neurobiological mechanism, it seems intuitive that the treatment for some of these symptoms would have an effect on the others. It would make sense for anti-seizure medications to also affect other manifestations of the disease in positive ways. However, unlike we are with tracking seizures, we are yet not very skilled in actively looking for these symptoms or tracking their evolution over time.
The first step to addressing the problem is to obtain some form of psychological baseline and an assessment on depression, anxiety, and suicidality in the clinic. Self-administered screening tools are widely available, easy to apply, and free for healthcare providers to use (6). These tools take a short time to score and may inform anti-seizure medication choice. They also allow for proactive followup, signaling the development or worsening of psychiatric symptoms and leading to timely intervention.
It may not be intuitive for many patients to report mood, emotional, or behavioral changes to their neurologists unless the provider takes an active role inquiring about them. In addition, patients may not think of reporting psychiatric symptoms as side effects of medications. They need to be educated about this possibility and given an action plan in case these symptoms arise or worsen. Keep in mind that prevention is the only possible intervention to combat deadly complications such as suicide.
Psychiatric side effects of anti-seizure medications are common (17.2%) and not always positive, even when seizures are controlled (7). They are a frequent reason for medication discontinuation. Psychiatric and behavioral side effects of levetiracetam are reported in up to 22% of patients (7), which is significantly higher than other anti-seizure medications. Carbamazepine, valproic acid, gabapentin, and lamotrigine have been associated with beneficial psychiatric and behavioral effects.
Guilfoyle et al. reported a step-based proactive approach for screening children and adolescents for comorbid behavioral and mood disorders, addressing the effects of AEDs on mood and depression. As reported in adults, the existence of premorbid psychiatric conditions seems to be the best predictor for the development of mood and behavioral side effects when medications are started. Children expressed more behavioral symptoms (irritability and agitation), while adolescents showed more mood-related symptoms as side effects of AEDs. This study highlights the need for establishing a psychological baseline and followup for children and adolescents with epilepsy. The baseline is instrumental at the time of choosing AEDs but also for evaluating side effects and detecting psycho-pathology in time to make treatment adjustments. Interestingly, contrary to the expected, Guilfoyle and colleagues did not find significant difference in children's behavioral side effects among anti-seizure medications popularly thought to have contrasting psychotropic side effects, such as valproic acid, levetiracetam, and carbamazepine.
Rocamora et al. prospectively evaluated the evolution of psychiatric symptoms in patients with focal epilepsy treated with lacosamide as an adjuvant therapy and tried to isolate the effect of lacosamide on mood and quality of life, independent of seizure control. They found significant improvement in depression, anxiety, and quality of life related to the medication. Prior studies (8, 9) have showed results in a similar direction, thereby strengthening the evidence in support of a positive psychotropic effect of lacosamide.
Knowing that both the underlying condition as well as our medication choice may have the ability to worsen or improve our patients’ psychopathology presents a challenge and an opportunity. The challenge is to proactively identify our patients at risk and start treatment when needed; the opportunity is to learn to use medications wisely to the maximum benefit for our patients while avoiding polypharmacy and medication interactions. We need to ensure that our interventions are not making the situation worse, no matter how well we achieve seizure control. We need to make sure our remedy is not worse than the disease.
Having effective treatment options that also have psycho-tropic benefits is a real advantage in the clinic—more so if satisfactory results are also achieved in seizure control.
Five ideas come to mind in putting this knowledge to use in the clinic scenario:
Psychiatric co-morbidities of epilepsy and anti-seizure medication psychiatric side effects may co-exist. Medication changes may be needed to address any active concerns.
The only way to evaluate a psychotropic result following any intervention is with proactive, appropriate, directed, and standardized followup.
Patients need to be educated about both possible psychiatric side effects and possible side benefits of anti-seizure medications.
Mood and behavioral changes may happen when starting a new medication and when adjusting doses or discontinuing medications as they might have been exerting a positive psychotropic side effect.
Be aware of vulnerable populations—such as children, adolescents, and the elderly—who may have atypical presentations of depression.