Can Acyclovir Change Your Mood?: Understanding Neuropsychiatric Side Effects

October 7, 2025 •

4 min read

While generally well-tolerated, psychiatric side effects associated with acyclovir therapy are very rare. For those asking, "Can acyclovir change your mood?", the answer is yes, but it typically only occurs in specific at-risk populations and is linked to acyclovir neurotoxicity.

Quick Summary

Although uncommon, acyclovir can cause neuropsychiatric symptoms, including mood changes, confusion, and hallucinations. These serious side effects are primarily linked to drug neurotoxicity, particularly in individuals with impaired kidney function, elderly patients, or those on high doses. Symptoms are generally reversible upon discontinuing the medication and managing the underlying cause.

Key Points

Acyclovir neurotoxicity is rare: Mood changes from acyclovir are an uncommon, but serious, side effect associated with drug neurotoxicity, not standard use.
Kidney function is a key risk factor: The most significant risk factor is impaired renal function, which causes a toxic metabolite (CMMG) to accumulate and enter the brain.
Symptoms range from mild to severe: Neuropsychiatric effects can include mood changes like agitation or depression, cognitive issues such as confusion, and in severe cases, hallucinations and delirium.
The virus itself can also affect mood: It is important to distinguish between drug-induced changes and the emotional stress (like anxiety or depression) that can result from a herpes diagnosis or even viral-induced neuroinflammation.
Symptoms are usually reversible: Discontinuation of the medication typically leads to the resolution of symptoms within several days.
Elderly and high-dose patients are vulnerable: Advanced age and high dosage regimens, particularly intravenous, increase the risk of neurotoxicity.

The Link Between Acyclovir and Neurotoxicity

Acyclovir, and its derivative valacyclovir, are widely used antiviral medications for treating herpes simplex (HSV) and varicella-zoster (VZV) infections. For the vast majority of patients, these drugs are well-tolerated. However, a small number of individuals may experience a rare but serious adverse effect known as acyclovir-induced neurotoxicity (AIN). This condition is characterized by a range of neuropsychiatric symptoms, including mood changes. The mechanism is primarily associated with the accumulation of a toxic metabolite, not the drug itself, and certain risk factors make it more likely to occur.

The Role of the Acyclovir Metabolite CMMG

When acyclovir is processed by the body, a small portion of it is converted into a metabolite called 9-carboxymethoxymethylguanine (CMMG). This metabolite is typically filtered out by healthy kidneys and excreted in the urine. However, in individuals with impaired kidney function, CMMG can build up in the bloodstream to toxic levels. It is believed that CMMG can then cross the blood-brain barrier more easily than acyclovir itself, entering the central nervous system (CNS). Elevated levels of CMMG in the cerebrospinal fluid (CSF) have been found to correlate strongly with the severity of neuropsychiatric symptoms in affected patients. This accumulation and subsequent CNS effects are the primary drivers of mood changes and other neurotoxic symptoms associated with acyclovir therapy.

Identifying Risk Factors for AIN

While anyone can theoretically experience AIN, certain patient populations are at a significantly higher risk due to factors that affect drug metabolism and clearance.

Primary risk factors include:

Impaired Renal Function: This is the most crucial risk factor. Patients with chronic kidney disease, end-stage renal disease, or those receiving dialysis are at a much higher risk of CMMG accumulation and, therefore, neurotoxicity.
Advanced Age: Elderly patients are more susceptible, not only because of a natural decline in renal function but also due to increased sensitivity to medications and potential comorbidities.
High Dosage: Administering high doses of acyclovir, particularly intravenously, increases the risk, especially if the dose is not appropriately adjusted for kidney function.
Immunocompromised State: Patients with weakened immune systems, such as those with HIV/AIDS or organ transplant recipients, may be more vulnerable.

Symptoms of Acyclovir-Induced Neurotoxicity

The mood and behavioral changes associated with AIN are part of a larger spectrum of neurological symptoms. These typically appear within a few days of starting treatment and can range from mild and reversible to severe.

Commonly reported neuropsychiatric symptoms include:

Mood Disturbances: This includes agitation, aggression, irritability, and depression.
Cognitive Changes: Confusion, disorientation, and delirium are frequently observed.
Psychotic Features: Some patients may experience hallucinations, including visual and auditory disturbances. Rare but specific symptoms like "death delusions" have also been documented.
Motor Disturbances: Tremors and unsteady movements (ataxia) are common, along with myoclonus (involuntary muscle jerks).
Altered Consciousness: Symptoms can progress from drowsiness to stupor and, in severe cases, coma.

Differentiating Acyclovir Effects from the Virus

It can be challenging to distinguish between the emotional effects of the drug and the stress associated with a herpes diagnosis or even neurological complications from the virus itself. Herpes viruses, particularly HHV-6, have been linked to neuroinflammation that may contribute to mood disorders like depression and bipolar disorder. However, key distinctions can be made.

Timing: AIN typically manifests acutely, within 1 to 3 days of initiating therapy. Emotional stress from a diagnosis may evolve over weeks or months.
Symptom Type: Specific symptoms like visual hallucinations, myoclonus, and rapid-onset confusion are more specific to drug neurotoxicity. Conversely, feelings of shame, anxiety, and depression are more common psychological reactions to the social stigma associated with herpes.
Viral Encephalitis: In cases of presumed viral encephalitis, the drug's neurotoxic symptoms could be mistaken for worsening viral infection. Elevated levels of CMMG in CSF can help confirm drug toxicity over viral etiology.

How Acyclovir Affects Mood vs. the Virus Itself


Feature	Acyclovir-Induced Neurotoxicity	Virus-Related Mood Changes	Herpes Encephalitis
Cause	Accumulation of toxic metabolite (CMMG) in CNS, often due to renal impairment.	Psychological stress, stigma, or potentially virus-induced neuroinflammation.	Direct viral invasion of the brain, causing inflammation.
Onset	Acute, typically within 1-3 days of starting treatment.	Variable; can be immediate emotional shock or develop over weeks/months.	Acute, often accompanied by high fever and severe headache.
Mood Symptoms	Agitation, aggression, depression, delirium, delusions.	Depression, anxiety, emotional distress, anger, shame.	Variable; can include confusion, seizures, altered consciousness.
Associated Symptoms	Hallucinations, myoclonus, tremors, confusion, ataxia.	Social withdrawal, difficulty coping, loss of self-esteem.	High fever, severe headache, neck rigidity, seizures, coma.
Resolution	Usually rapid after drug discontinuation or dialysis.	Gradually improves over time with counseling and acceptance.	Requires aggressive antiviral therapy and supportive care.

Management and Recovery

If AIN is suspected, the most important step is immediate medical attention. The antiviral medication must be discontinued promptly. For less severe cases, stopping the drug is often sufficient for a full recovery. In patients with severe renal impairment, particularly those on dialysis, symptoms may appear sooner and require more drastic intervention. In these instances, hemodialysis may be necessary to rapidly clear the CMMG metabolite from the blood. Recovery typically occurs within a few days to a week after treatment cessation, although some individuals may require longer.

Conclusion

While acyclovir change your mood is a rare phenomenon, it is a significant potential risk for specific, vulnerable populations, particularly those with reduced kidney function. The side effects, ranging from agitation and depression to confusion and hallucinations, are a manifestation of drug neurotoxicity caused by the accumulation of a toxic metabolite, CMMG. It is critical for both patients and healthcare providers to recognize the risk factors and symptoms, differentiating them from other potential causes of mood changes related to the virus or emotional distress. Prompt discontinuation of the medication and appropriate supportive care typically leads to a full recovery from these adverse neurological effects.

American Sexual Health Association: Emotional Issues with Herpes

Frequently Asked Questions

No, mood changes associated with acyclovir are a very rare and serious side effect, typically occurring as part of a broader syndrome called acyclovir-induced neurotoxicity, not in most patients.

Mood changes are caused by a rare build-up of a toxic metabolite of acyclovir called CMMG in the central nervous system. This typically happens in patients with impaired kidney function who cannot clear the substance from their bodies effectively.

Patients most at risk include the elderly, those with kidney disease or impaired renal function, and individuals receiving high doses of the drug.

Drug-induced neurotoxicity typically causes acute, rapid-onset symptoms like confusion, agitation, or hallucinations within a few days of starting the medication. Viral-related distress is often a longer-term emotional reaction to the diagnosis.

You should contact your doctor immediately. If acyclovir-induced neurotoxicity is suspected, the medication may need to be discontinued to prevent the condition from worsening.

In most cases, the neuropsychiatric side effects, including mood changes, are temporary and fully reversible upon stopping the medication.

While less common than in those with kidney impairment, there are rare case reports of neuropsychiatric adverse events in patients with normal renal function, suggesting that high doses alone can sometimes trigger the reaction.