Post-Ictal Psychosis

What Causes Post-Ictal Psychosis?

The cause of PIP is unknown. Some studies have shown unusual patterns of brain structure and activity in people with the disorder, but it is unclear whether these characteristics cause the symptoms.

People with epilepsy and a family history of psychiatric disorders appear to be at a higher risk of developing PIP. However, a link between PIP and any other mental illness has not been definitively established.

Is Post-Ictal Psychosis Hereditary?

PIP does not appear to be a directly inherited disorder. However, epilepsy itself sometimes has a genetic component, so inherited factors can increase a person’s risk of developing PIP. In addition, people with a family history of psychiatric disorders are also at higher risk, suggesting that some genetic component(s) may increase a person’s susceptibility to PIP.

Genetic factors influence whether someone will develop epilepsy. The disorder doesn’t result from a single gene. It can happen to anyone, at any age. If a close relative, such as a parent or sibling, has epilepsy, an individual may be at higher risk for epilepsy than someone with no family history. However, the chance of passing epilepsy down through generations is low.

If a parent has epilepsy, there is a 9%–12% chance that the child will also have epilepsy. Although most siblings of a child with epilepsy do not develop the disorder, brothers and sisters have a higher risk of epilepsy. In addition, if one twin has idiopathic epilepsy, meaning it arises for no identifiable reason, the identical twin is also likely to develop the disorder.

How Is Post-Ictal Psychosis Detected?

Warning signs sometimes precede PIP episodes in the hours before the onset of PIP symptoms. Psychosis can sometimes be prevented or relieved if antipsychotic medications are administered early on, making it vital to spot these signs when possible.

Early warning signs of PIP can include:

• Insomnia
• Restlessness
• Irritability

How Is Post-Ictal Psychosis Diagnosed?

A doctor may suspect PIP when a patient with epilepsy exhibits a distinctive cluster of symptoms. It’s possible to diagnose PIP when the symptoms meet the disorder’s diagnostic criteria, which include:

• Psychosis occurs within a week after a seizure or cluster of seizures.
• The psychotic episode lasts between 24 hours and three months.
• There is no evidence of a reaction to anticonvulsant medications, head injury, drug or alcohol intoxication, or history of another condition called interictal psychosis.

How Is Post-Ictal Psychosis Treated?

Treatment of PIP typically involves using medication to treat both the underlying seizures and the psychiatric symptoms of the disorder. Anticonvulsant drugs effectively control seizures in many cases, and therapies such as deep brain stimulation may help people with drug-resistant seizures.

Antipsychotic drugs or benzodiazepines have proven effective in treating the psychotic symptoms of PIP. Many doctors recommend using medications as early as possible when the disorder’s warning signs (e.g., insomnia) emerge. Some doctors recommend that people with a history of repeated PIP episodes take medications regularly as a preventive measure. It is essential to follow your doctor’s treatment plan.

How Does Post-Ictal Psychosis Progress?

About half of people who experience one PIP episode will experience more episodes later. The average rate of occurrence is 2-3 episodes per year.

As many as a quarter of people with PIP will eventually develop interictal psychosis (IIP). IIP is a condition in which psychotic episodes occur between seizures without any apparent connection to seizure activity. IIP is a serious condition that requires regular treatment with medications.

PIP episodes raise the risk of severe consequences such as:

• Violence and assault
• Homicide
• Suicide

How Is Post-Ictal Psychosis Prevented?

In most cases, PIP cannot be prevented, but the management of seizures and treatment of any co-existing mental health symptoms may help control PIP episodes.

Post-Ictal Psychosis Caregiver Tips

PIP poses a danger to both the sufferer and those around them. One study found that nearly a quarter of PIP episodes involved violence directed at people around the sufferer, and about seven percent of cases involved suicidal behavior. In light of the risks, caregivers need to be aware of the dangers. It is also crucial to be alert for the warning signs of an impending episode and seek medical help immediately.

Many people with epilepsy and PIP also suffer from other brain and mental health-related issues, a condition called co-morbidity. Here are a few of the disorders commonly associated with epilepsy:

• Many people with epilepsy also suffer from attention-deficit/hyperactivity disorder (ADHD) or learning disabilities.
• People with epilepsy are at increased risk of developing psychotic disorders, such as schizophrenia.
• Autism spectrum disorder, Alzheimer’s disease, and other forms of dementia are more common in people with epilepsy.
• Other mental disorders, including interictal behavior syndrome, are only experienced by people with epilepsy.

Post-Ictal Psychosis Brain Science

Some studies have found structural differences between the brains of people with PIP and healthy brains. These structural differences are similar to brain abnormalities observed in schizophrenia patients, suggesting a link between the two disorders.

Atypical brain structures in PIP patients include:

• Larger than usual ventricles (spaces inside the brain)
• Smaller temporal lobe
• Smaller frontoparietal lobe
• Smaller superior temporal gyrus

Post-Ictal Psychosis Research

Title: Ketogenic Diet for Psychotic Disorders (PsyDiet)

Stage: Recruiting 

Principal Investigator: Anu Ruusunen, PhD   

Kuopio University Hospital

Kuopio, Finland

Disturbances in glucose metabolism and glutamate neurotransmission feature in the pathophysiology of psychotic disorders. A ketogenic diet (KD) is a high-fat, low-carbohydrate diet that restricts glucose and forces the metabolism of ketones, which serve as alternative energy substrates for the brain. KD is an established treatment for intractable epilepsy. However, we lack the RCT evidence regarding the potential effects of KD on psychotic symptoms in humans.

This randomized, controlled pilot study aims to investigate:

• feasibility of a Modified Ketogenic Diet (MKD) intervention protocol in psychotic inpatients,
• potential impact of MKD intervention on psychotic symptoms, depressive and anxiety symptoms, and functioning in patients with psychotic symptoms / psychotic disorder.

A 6-week randomized KD pilot study will be conducted in psychotic inpatients (aimed n=40) at Kuopio University Hospital, Finland. In the KD group, carbohydrate consumption is limited to 15-20 g/day to activate ketosis. The control group will have their ordinary hospital meals. The Structured Clinical Interview for DSM Axis I disorders (SCID-I) and the Positive and Negative Syndrome Scale (PANSS) will assess current psychotic disorders and psychotic symptoms. Blood glucose, lipid, ketone body levels, and weight will be measured. Background variables (socioeconomic factors, co-morbidities, obtained treatments including medications, and health behaviors including diet) will be documented.

Title: R33: Levetiracetam in Early Psychosis

Stage: Recruiting 

Principal Investigator: Donald Goff, MD

NYU Langone Health

New York, NY

This is a 12-week study of levetiracetam added to a second-generation antipsychotic in early psychosis patients who have been ill for less than five years and continue to experience psychotic symptoms despite at least eight weeks of antipsychotic treatment. Levetiracetam (Keppra) is a medication approved for the treatment of epilepsy; it reduces excessive activity in the brain. This study will test the hypotheses that adding levetiracetam will improve psychotic symptoms that are unresponsive to antipsychotic treatment and protect the brain from atrophy (volume loss).

Participants will complete screening and baseline visits before being randomized in a 2:1 ratio to levetiracetam or placebo added to the antipsychotic medication. They will complete weekly study visits for the first four weeks (Baseline, Weeks 2-4) and then additional visits at Week 6, 8, and 12. Participants will be studied both by assessing change in symptom severity and cognitive performance over the 12 weeks as well as using an imaging measure of hippocampal volume integrity at baseline and week 12. After completing Week 12 or deciding to withdraw prematurely from the study, participants will complete a nine-day medication tapering regimen.

Title: A Computerized CBTi for Insomnia in Epilepsy

Stage: Recruiting 

Principal Investigator: Nancy Foldvary-Schaefer, DO

The Cleveland Clinic

Cleveland, OH

A growing interest in the relationship between epilepsy and sleep has resulted in several investigations demonstrating the high prevalence of sleep disturbances and disorders in people with epilepsy (PWE). PWE frequently report daytime sleepiness, insomnia, and other sleep problems.

Insomnia is among the most common sleep complaint in PWE. The prevalence of moderate-to-severe insomnia using the ISI ranges from 15% to 51%. A recent case-control study found an association between insomnia symptom severity and poorer seizure control. Difficulty maintaining sleep is the most common insomnia presentation, followed by difficulty initiating sleep. Both patterns are accompanied by a decrease in total sleep time and an increase in the number of awakenings, arousals, and wake time after sleep onset, leading to a state of relative sleep deprivation. Like epilepsy, insomnia disorders are commonly associated with co-morbid depression in the general population, confirmed in a cohort of adults with epilepsy from our own epilepsy center. In turn, treatment of depression has been shown to improve insomnia in the general population. Further, improved seizure control has been observed following treatment of other co-morbid sleep disorders such as obstructive sleep apnea and poor sleep hygiene. Innovative sleep treatments for PWE are needed.

To date, there are no studies exploring sleep and seizure outcomes with the treatment of insomnia in PWE. Cognitive Behavioral Therapy for Insomnia(CBT-i) is generally the preferred initial treatment for most cases of primary insomnia. CBT-i examines and promotes modifications in thoughts and behaviors that perpetuate insomnia. The validity of CBT-i has been well established, and the American College of Physicians has acknowledged CBT-i as the first-line therapy for insomnia with treatment effects that outlast those of sedative-hypnotic medications. Despite its established efficacy, CBT-i is not widely accessible due to the lack of trained clinicians, stigmatization in receiving psychological services, geographical remoteness to qualified providers, and cost. Treatment typically involves a series of up to 10 visits at weekly or biweekly intervals.

In recent years, CCBT-i programs have been developed that offer web-based treatment. One such program is GoTo sleep (GTS), developed and validated by investigators at the Cleveland Clinic. GTS constitutes six weeks of therapy based on the principles and methods of CBT-i presented as a series of daily lessons, learnable skills, and personalized recommendations supported by graphics, animations, audio, and video. The program includes the basic elements of CBT-i, including sleep hygiene, sleep restriction, stimulus control, cognitive restructuring, and relaxation training. The efficacy of CCBT-i has been demonstrated in several randomized controlled trials involving patients with primary insomnia, including one using GTS, where the program was found to be superior to usual care (sleep hygiene instruction) after six weeks of therapy. Further, we recently conducted a pilot study comparing GTS and standard sleep hygiene instruction in Parkinson’s disease patients with insomnia and found a greater reduction in ISI scores with CCBT-i (-7.9 vs. -3.5; p=0.03).

Given the prevalence of insomnia in epilepsy and the known association between seizure occurrence and sleep impairment, the investigators hypothesize that treating insomnia with CCBT-i will improve insomnia symptoms and seizure control in PWE.