Spritam Side Effects: What to Expect and When to Call Your Doctor

Spritam (levetiracetam) is the same active ingredient as Keppra — just in a 3D-printed rapid-dissolve tablet form. That means its side effect profile is identical to standard levetiracetam. For most patients, side effects are manageable or improve over time. But there are some important warnings — including an FDA class-wide warning for all anti-epileptic drugs — that every patient and caregiver should know.

Common Side Effects in Adults

In clinical studies of adult patients, the following side effects occurred in at least 5% more patients on levetiracetam than on placebo:

Somnolence (sleepiness) — 15%. The most common adult side effect. About 3% of patients discontinued treatment because of it. Typically worse early in treatment and often improves over time.

Asthenia (weakness, tiredness). General fatigue and muscle weakness are reported by a meaningful proportion of patients, especially during the first weeks of therapy.

Infection. Upper respiratory infections occurred more frequently in levetiracetam-treated patients, though this may be partially related to the immune effects of seizure activity itself.

Dizziness. More common in the early weeks of treatment. Patients should be cautious about driving until they know how Spritam affects them.

Coordination difficulties / ataxia. About 3.4% of adult patients reported ataxia, abnormal gait, or incoordination, compared to 1.6% on placebo. Most common in the first 4 weeks of treatment.

Common Side Effects in Children

Children's side effect profile differs somewhat from adults. In pediatric clinical studies, the most common Spritam side effects were:

Fatigue

Aggression — Behavioral worsening, particularly aggressive behavior, is notably more common in children. In one study, 11% of levetiracetam-treated pediatric patients experienced behavioral symptoms leading to dose reduction or discontinuation, compared to 6% on placebo. In infants under 4 years, irritability was reported in 12% vs. 0% on placebo.

Nasal congestion

Decreased appetite

Irritability

Serious Side Effects — What to Watch For

The following serious side effects require prompt medical attention:

Behavioral and psychiatric symptoms. Aggression, agitation, anger, anxiety, apathy, depression, hostility, and irritability have all been reported. Psychosis (rare, 0.3% in adults) can develop, typically within the first week and resolving within 1–2 weeks of stopping the drug. Contact your doctor if you notice significant mood or behavior changes.

Suicidal ideation (class-wide FDA warning). All antiepileptic drugs, including Spritam, carry an FDA warning about increased risk of suicidal thoughts and behavior. Pooled analysis of 199 clinical trials showed patients on AEDs were approximately twice as likely to report suicidal thoughts vs. placebo. Patients and caregivers should watch for unusual changes in mood, depression, or thoughts of self-harm and report them immediately.

DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms). An FDA alert was issued in December 2023 for DRESS with levetiracetam. DRESS is a serious hypersensitivity reaction that typically presents with fever, rash, swollen lymph nodes, and internal organ involvement (liver, kidneys, lungs). It can be fatal if not caught early. If you develop a fever with a rash, contact your doctor immediately.

Stevens-Johnson Syndrome (SJS) / Toxic Epidermal Necrolysis (TEN). Rare but severe skin reactions. The median onset is 14–17 days into treatment but can appear months later. Symptoms include blistering, skin peeling, and painful rashes. Stop the medication and seek emergency care immediately if these occur.

Anaphylaxis / severe allergic reaction. Severe allergic reactions including anaphylaxis and facial swelling can occur at any time during treatment. Call 911 immediately if you experience difficulty breathing, severe swelling of the face, lips, or throat.

Hematologic changes. Decreased white blood cell, red blood cell, and neutrophil counts have been reported, including rare cases of agranulocytosis. If you have unusual weakness, recurring infections, or bruising/bleeding, contact your doctor.

The "Keppra Rage" Phenomenon

Many patients and caregivers have heard of "Keppra rage" — a colloquial term for the irritability, aggression, and emotional volatility that some levetiracetam users experience. This is real and well-documented in the medical literature. It's believed to be related to how levetiracetam affects the central nervous system. Behavioral side effects are one of the most common reasons patients discontinue levetiracetam.

If you or your child is experiencing significant behavioral changes on Spritam, talk to your neurologist. Options include dose adjustment, switching to a related medication with a lower behavioral side effect profile (such as brivaracetam / Briviact), or adding a vitamin B6 (pyridoxine) supplement, which some clinicians use to reduce irritability, though this is off-label.

When to Call Your Doctor

Any new rash, especially with fever or swollen glands — STOP medication and call immediately

Thoughts of suicide, self-harm, or significant depression

Significant behavioral changes (severe aggression, psychosis-like symptoms)

Difficulty breathing or severe facial swelling — call 911

Unusual bruising, bleeding, or persistent infections

Worsening seizures after starting or changing Spritam dose

Related guides: Spritam Drug Interactions and What Is Spritam? Uses, Dosage, and What You Need to Know.