Neuropsychiatric adverse effects of interferon-alpha: recognition and management.

Charles L Raison, Marina Demetrashvili, Lucile Capuron, Andrew H Miller
CNS Drugs. 2005-01-01; 19(2): 105-123
DOI: 10.2165/00023210-200519020-00002

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1. CNS Drugs. 2005;19(2):105-23.

Neuropsychiatric adverse effects of interferon-alpha: recognition and management.

Raison CL(1), Demetrashvili M, Capuron L, Miller AH.

Author information:
(1)Department of Psychiatry and Behavioral Sciences, Emory University School of
Medicine, Atlanta, Georgia 30322, USA.

Recombinant preparations of the cytokine interferon (IFN)-alpha are increasingly
used to treat a number of medical conditions, including chronic viral hepatitis
and several malignancies. Although frequently effective, IFN alpha induces a
variety of neuropsychiatric adverse effects, including an acute confusional state
that develops rapidly after initiation of high-dose IFN alpha, a depressive
syndrome that develops more slowly over weeks to months of treatment, and manic
conditions most often characterised by extreme irritability and agitation, but
also occasionally by euphoria. Acute IFN alpha-induced confusional states are
typically characterised by disorientation, lethargy, somnolence, psychomotor
retardation, difficulties with speaking and writing, parkinsonism and psychotic
symptoms. Strategies for managing delirium should be employed, including
treatment of contributing medical conditions, use of either typical or atypical
antipsychotic agents and avoidance of medications likely to worsen mental status.
Significant depressive symptoms occur in 21-58% of patients receiving IFN alpha,
with symptoms typically manifesting over the first several months of treatment.
The most replicated risk factor for developing depression is the presence of mood
and anxiety symptoms prior to treatment. Other potential, but less frequently
replicated, risk factors include a past history of major depression, being female
and increasing IFN alpha dosage and treatment duration. The available data
support two approaches to the pharmacological management of IFN alpha-induced
depression: antidepressant pretreatment or symptomatic treatment once IFN alpha
has been initiated. Pretreatment might be best reserved for patients already
receiving antidepressants or for patients who endorse depression or anxiety
symptoms of mild or greater severity prior to therapy. Several recent studies
demonstrate that antidepressants effectively treat IFN alpha-induced depression
once it has developed, allowing the vast majority of subjects to complete
treatment successfully. Recent data suggest that IFN alpha-induced depression may
be composed of two overlapping syndromes: a depression-specific syndrome
characterised by mood, anxiety and cognitive complaints, and a neurovegetative
syndrome characterised by fatigue, anorexia, pain and psychomotor slowing.
Depression-specific symptoms are highly responsive to serotonergic
antidepressants, whereas neurovegetative symptoms are significantly less
responsive to these agents. These symptoms may be more effectively treated by
agents that modulate catecholaminergic functioning, such as combined
serotonin-noradrenaline (norepinephrine) antidepressants, bupropion,
psychostimulants or modafinil. Additional factors to consider in selecting an
antidepressant include potential drug-drug interactions and adverse effect
profile. Finally, IFN alpha appears capable of inducing manic symptoms. Mania,
especially when severe, is a clinical emergency. When this occurs, IFN alpha and
antidepressants should be stopped, an emergency psychiatric consultation should
be obtained, and treatment with a mood stabilizer should be initiated.

DOI: 10.2165/00023210-200519020-00002
PMCID: PMC1255968
PMID: 15697325 [Indexed for MEDLINE]

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