Prevalence and detection of neuropsychiatric adverse effects during hepatitis C treatment.
BACKGROUND
Current treatment combinations for chronic hepatitis C virus infection still include pegylated interferon and ribavirin despite the new therapeutic options available. Interferon-based treatments are associated with a high incidence of adverse effects. Central nervous system events are among the most frequent adverse drug reactions and their influence on treatment adherence and effectiveness is controversial.


OBJECTIVE
The aim of the study was to evaluate neuropsychiatric adverse effects of interferon-based treatment for chronic hepatitis C in standard multidisciplinary clinical practice. Risk factors for these adverse effects and their impact on adherence and sustained viral response were also evaluated. Setting Ambulatory care pharmacy in coordination with the liver unit and the infectious diseases unit at a 650-bed tertiary university hospital.


METHODS
We included all consecutive patients with chronic hepatitis C who completed treatment with pegylated interferon and ribavirin between 2005 and 2013. All patients underwent a multidisciplinary follow-up during treatment.


METHODS
Neuropsychiatric adverse effects were evaluated in relation to severity, management and outcome. The presence of anxiety and depression was evaluated by means of specific tests.


RESULTS
A total of 717 treatments in 679 patients were included. During treatment, we detected 1679 neuropsychiatric adverse effects in 618 patients (86.2 %), generating 1737 clinical interventions. Fifty-seven (3.3 %) neuropsychiatric adverse effects were severe and 2 (0.1 %) were life-threatening (suicidal attempts). Most neuropsychiatric adverse effects (1555 events, 92.6 %) resolved without sequelae. Psychiatric medication was required in 289 patients (40.3 %). Sustained viral response was achieved in 400 cases (55.8 %) and was associated with adherence (OR = 1.942, 95 % CI = 1.235-3.052, p = 0.004). A multivariate analysis did not show any relationship between neuropsychiatric adverse effects and treatment adherence or sustained viral response. A psychiatric history was a strong risk factor for depression, anxiety and other psychiatric disorders during treatment.


CONCLUSIONS
Neuropsychiatric adverse effects during interferon-based treatments in patients with chronic hepatitis C were common but mostly mild or moderate. Early detection and accurate multidisciplinary management avoided treatment discontinuation, ensuring adherence and attaining sustained viral response. The identified risk factors could be used to determine patients eligible for interferon-free combinations, thus optimizing health system economics.
Pharmacy Department, Hospital de la Santa Creu i Sant Pau, Sant Antoni Mª Claret, 167, 08025, Barcelona, Spain. mmassip@santpau.cat.
Montserrat
M
Masip
Pharmacy Department, Hospital de la Santa Creu i Sant Pau, Sant Antoni Mª Claret, 167, 08025, Barcelona, Spain.
Laura
L
Tuneu
Pharmacy Department, Hospital de la Santa Creu i Sant Pau, Sant Antoni Mª Claret, 167, 08025, Barcelona, Spain.
Neus
N
Pagès
Gastroenterology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.|CIBERehd, Madrid, Spain.
Xavier
X
Torras
Gastroenterology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Adolfo
A
Gallego
Infectious Diseases Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Josep Maria
JM
Guardiola
Pharmaceutical Care Research Group, School of Pharmacy, University of Granada, Granada, Spain.
María José
MJ
Faus
Pharmacy Department, Hospital de la Santa Creu i Sant Pau, Sant Antoni Mª Claret, 167, 08025, Barcelona, Spain.
Maria Antònia
MA
Mangues
D000328:Adult; D000367:Age Factors; D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006304:Health Status; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D055118:Medication Adherence; D001523:Mental Disorders / Q000139:chemically induced*; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000627:therapeutic use; D015995:Prevalence; D012367:RNA, Viral; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use; D012307:Risk Factors; D012720:Severity of Illness Index; D012737:Sex Factors
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a
Depression; Detection; Hepatitis C treatment; Multidisciplinary management; Neuropsychiatric adverse effects; Pegylated interferon alpha; Prevalence; Ribavirin; Spain