Table 4
Which psychotropics carry ‘black-box’ warnings?
| Warning | Class or medication affected | Comments |
|---|---|---|
| Suicidality | Antidepressants Antipsychotics indicated for mood disorders Anticonvulsants | See ‘Black-box warnings’ |
| Serious, life-threatening rashes such as Stevens-Johnson syndrome or toxic epidermal necrolysis | Lamotrigine Carbamazepine | Lamotrigine’s risk of severe dermatologic reactions necessitates slow titration during drug initiation Carbamazepine warning includes a recommendation for genetic screening in Asian patients because Stevens-Johnson syndrome is associated with the HLA-B*1502 allele found primarily in the Asian population |
| Increased mortality in elderly patients with dementia-related psychosis | Antipsychotics | A study of >10,000 geriatric patients with dementia showed mortality rates of 22.6% to 29.1% among those who took antipsychotics compared with 14.6% for patients taking other psychiatric medications. When antipsychotics are used in older adults, well-documented informed consent from the patient or substitute decision-maker is required |
| Other effects | Clozapine | Agranulocytosis occurs in 1% to 2% of clozapine patients, necessitating WBC/ANC monitoring Clozapine-induced myocarditis, generally accompanied by peripheral eosinophilia, usually occurs within the first 2 months of treatment, and can result in significant mortality from resultant cardiomyopathy. Early warning signs of fever, fatigue, and tachycardia are easily mistaken for the more benign effects of clozapine titration Seizures are more likely with higher doses. Cautious use is advised with patients who have an underlying seizure disorder Other cardiovascular and respiratory effects: Hypotension has been associated with rapid initial titration. Cardiac and respiratory arrest and circulatory collapse have occurred rarely. Respiratory complications are more likely when clozapine is used in combination with benzodiazepines |
| ANC: absolute neutrophil count; WBC: white blood cell Source: References 5,14-16 | ||
Other complications
Hematologic effects. All classes of psychotropics carry a risk (1 to 2 cases per year per 100,00 patients) of serious hematologic complications, including neutropenia, agranulocytosis, eosinophilia, thrombocytopenia, purpura, and anemia.17 Agranulocytosis has been associated most commonly with clozapine, carbamazepine, and typical antipsychotics.17 SSRIs, which are widely prescribed, are associated with increased risk of bruising and bleeding. Patients with bleeding or platelet disorders are at an increased risk for these complications.17
Seizures. Several classes of psychotropics are associated with an increased risk of seizures. Among antipsychotics, clozapine and chlorpromazine are the most seizurogenic.18 Among antidepressants, bupropion and clomipramine are most likely to lower seizure thresholds.18 Psychotropics’ seizure-inducing effects are dose-related. Vulnerability to seizures while taking psychotropics is related to having a history of epilepsy or brain injury.18 Seizures also can occur when benzodiazepines or anticonvulsants are withdrawn too quickly.
Heat stroke. Although a rare occurrence, psychotropics with anticholinergic side effects can contribute to heat stroke. Older patients are particularly vulnerable to the risk of body temperature dysregulation.19
Ketoacidosis and hyperosmolar coma. Medication-related deaths have occurred as a result of ketoacidosis and hyperosmolar coma associated with atypical antipsychotics. These hyperglycemia-related fatalities are most likely with clozapine and olanzapine.20
Hip fractures and falls. Geriatric patients are vulnerable to falls and resultant hip fractures related to use of TCAs, SSRIs, benzodiazepines, and antipsychotics. This is not a trivial matter; hip fractures increase the mortality rate by 12% to 20% in the year after the injury.21 The risk of falls is related to sedation, orthostatic hypotension, arrhythmias, and confusion associated with psychotropics.21,22
Akathisia and suicide. Unrecognized or undertreated akathisia is most commonly associated with antipsychotics, but also can occur with SSRIs. Although akathisia is commonly thought of as a motor syndrome of restlessness, patients may find the less-recognized psychic symptoms of increased inner turmoil and hallucinations just as distressing. This complex of symptoms is associated with an increased risk of suicide.23 If discontinuing the offending agent is not feasible, akathisia can be treated with beta blockers, benzodiazepines, or anticholinergics.24
Hepatotoxicity. Hepatotoxicity from psychotropics occurs in only a small percentage of patients, and can range from transient elevations in liver enzymes to fulminant liver failure. Adverse hepatic effects may be a manifestation of a hypersensitivity reaction accompanied by rash and eosinophilia.25 MAOIs and TCAs can cause cholestatic liver injury, whereas nefazodone has been associated with fulminant liver failure. Other psychotropics—including SSRIs, antipsychotics, benzodiazepines, and older antiepileptics—can cause negative hepatic effects but rarely are associated with acute liver failure.25,26 Although few medications can cause complete liver failure on their own, hepatotoxicity from medications may precipitate severe, potentially fatal outcomes in patients with underlying liver diseases such as hepatitis and cirrhosis. Additive hepatotoxicity from multiple medications also can be problematic. Although psychotropic-induced hepatotoxicity is rare, assess psychotropic doses in patients with liver dysfunction, because drug clearance may be altered, which increases the risk for other serious adverse events.25