Understanding Haldol and Rhabdomyolysis
Haloperidol, sold under the brand name Haldol, is a typical antipsychotic medication used to treat a variety of psychiatric conditions, including schizophrenia [1.2.6]. While effective, it is associated with a range of side effects. One of the more severe, though uncommon, adverse effects is rhabdomyolysis [1.2.4].
Rhabdomyolysis is a clinical syndrome characterized by the rapid breakdown (lysis) of skeletal muscle tissue [1.4.7]. This process releases intracellular muscle components, such as myoglobin and creatine kinase (CK), into the bloodstream [1.3.3]. The release of these substances can lead to serious complications, including electrolyte imbalances, and most notably, acute kidney injury (AKI) as myoglobin can be toxic to the kidneys [1.4.2, 1.4.8].
The Link: How Can Haldol Cause Rhabdomyolysis?
Case reports and pharmacovigilance data confirm a link between haloperidol and the development of rhabdomyolysis [1.2.4, 1.3.1]. This adverse effect has been observed with both oral and intramuscular long-acting (decanoate) forms of the medication [1.2.4]. The rhabdomyolysis can occur in two primary contexts: as a component of Neuroleptic Malignant Syndrome (NMS), or as a separate event without the other classic signs of NMS [1.2.3, 1.2.4].
The Role of Neuroleptic Malignant Syndrome (NMS)
NMS is a life-threatening neurological emergency most often caused by antipsychotic medications [1.4.2]. Haloperidol is one of the drugs most commonly associated with NMS [1.2.3]. The syndrome is defined by a cluster of symptoms:
- Hyperthermia: High fever
- Muscle Rigidity: Severe stiffness, often described as "lead-pipe" rigidity
- Altered Mental Status: Confusion, agitation, or coma
- Autonomic Dysfunction: Irregular pulse, variable blood pressure, and sweating [1.4.1]
Rhabdomyolysis is a frequent complication of NMS, resulting from intense muscle rigidity and hyperthermia, which lead to muscle cell breakdown [1.4.1, 1.4.4].
Rhabdomyolysis Without NMS
Several case studies have documented patients developing rhabdomyolysis after taking haloperidol without exhibiting the full criteria for NMS [1.2.3, 1.2.4]. This suggests that haloperidol may have a direct toxic effect on muscle tissue, independent of the mechanisms that cause NMS's other symptoms [1.2.6]. The exact mechanism for non-NMS rhabdomyolysis is not fully understood, but leading theories propose it involves the blockade of dopamine and/or serotonin receptors [1.3.4]. This blockade might disrupt normal muscle function, potentially by altering calcium release within muscle cells, leading to increased muscle contractility and eventual breakdown [1.3.2].
Risk Factors and Clinical Presentation
Several factors can increase the risk of developing antipsychotic-induced rhabdomyolysis:
- Polypharmacy: Taking multiple antipsychotic agents simultaneously [1.5.1].
- Dosage: A dose increase can sometimes precede the onset of symptoms [1.2.2].
- Method of Administration: Intramuscular injections can cause localized muscle injury, which may contribute to the risk [1.3.2]. The long-acting decanoate injection has a half-life of about three weeks, which can lead to prolonged elevation of CK levels [1.2.6].
- Comorbidities: Concurrent infections (like COVID-19), dehydration, and excessive physical exertion can exacerbate the risk [1.3.1, 1.5.3].
- Substance Use: Concurrent use of alcohol or illicit drugs like cocaine and amphetamines is a significant risk factor for rhabdomyolysis [1.5.3, 1.5.4].
Signs and symptoms that should prompt immediate medical evaluation include:
- Muscle pain, tenderness, or weakness [1.4.8].
- Dark, reddish-brown, or tea-colored urine (caused by myoglobin) [1.2.3, 1.4.8].
- Fatigue and generalized malaise [1.2.4].
- Reduced urine output [1.4.8].
Diagnosis is confirmed through blood tests showing highly elevated levels of creatine kinase (CK) and urine tests positive for myoglobin [1.2.2]. Treatment involves immediate discontinuation of the offending drug (haloperidol) and aggressive intravenous hydration to protect the kidneys from damage [1.3.1, 1.4.4].
Comparison of Antipsychotics and Rhabdomyolysis Risk
While this article focuses on Haldol (a typical antipsychotic), both typical and atypical antipsychotics are associated with rhabdomyolysis. A 2025 study analyzing the FDA Adverse Event Reporting System (FAERS) provided insights into the relative risk for several atypical antipsychotics, though it did not include typicals like haloperidol in its primary comparison table [1.6.2].
| Antipsychotic (Atypical) | Reported Cases (FAERS) [1.6.2] | Relative Risk Signal (ROR) [1.6.2] | Median Onset Time (Days) [1.6.2] |
|---|---|---|---|
| Olanzapine | 621 | 4.02 | 174.0 |
| Quetiapine | 655 | 3.81 | 31.0 |
| Ziprasidone | 67 | 2.76 | 25.0 |
| Risperidone | 362 | 2.12 | 11.0 |
| Aripiprazole | 364 | 2.00 | 35.5 |
| Clozapine | 290 | 1.47 | 595.0 |
It is important to note that case reports specifically mention haloperidol, clozapine, olanzapine, and risperidone as causes of rhabdomyolysis [1.6.6]. Another case report suggests that typical antipsychotics like haloperidol may have a lower risk profile compared to some atypicals, but the mechanism remains unclear [1.6.4].
Conclusion
The evidence clearly indicates that Haldol (haloperidol) can cause rhabdomyolysis, a serious and potentially life-threatening condition. This can happen as part of Neuroleptic Malignant Syndrome or as an isolated event, possibly due to direct muscle toxicity. The risk is heightened by factors such as high dosage, polypharmacy, and co-existing medical conditions. Due to this risk, clinicians and patients should be vigilant for symptoms like muscle pain and dark urine. Prompt recognition, discontinuation of the drug, and aggressive supportive care are critical to preventing severe complications like acute kidney failure.
For more detailed information on drug-induced rhabdomyolysis, consult authoritative resources such as the National Institutes of Health (NIH).
