Immunological response to Hepatitis B vaccination in obsessive compulsive disorder patients receiving high doses of serotonin reuptake inhibitors

Serotonin reuptake inhibitors (SRI*s) such as paroxetine and venlafaxine are
commonly prescribed drugs in the treatment of psychiatric disorders. The main
indications for these drugs are major depression and anxiety disorders such as
obsessive compulsive disorder (OCD). Although the adverse effect profile of
SRI*s is well known, there is some concern about the impact of these drugs on
immunity. Both in vitro and in vivo evidence shows that SRI*s have a negative
effect on cellular immune responses. For instance, SRI*s supress in vitro
mitogen-induced lymphocyte proliferation and induce apoptosis in activated
lymphocytes.1 Also, in vivo administration of SRI*s can impair mitogen-induced
lymphocyte proliferation both in animals2 and in humans3. Impairment of the
immunological suppression of herpes simplex virus in patients treated with
SRI*s has also been reported.4

OCD is a psychiatric condition characterized by intrusive, unwanted and
recurrent thoughts (obsessions) and/or repetitive ritualistic behaviors
(compulsions). The most widely prescribed drugs for OCD are SRI*s, and the
condition generally requires treatment with doses 2-3 times higher than the
doses administered for major depression. Whereas paroxetine is usually dosed at
20 mg/d for depression, OCD patients often receive doses up to 60 mg/d. Thus,
these patients are in relatively high risk to encounter immunological
disturbances due to SRI-treatment.

Although immune parameters such as cytokine production, NK-cell activity and
peripheral blood cell counts in OCD patients do not seem to be altered by
paroxetine or venlafaxine in the absence of an immunological stimulus5, it is
possible that SRI*s may supress the efficient mounting of an immune response
when an immunological challenge, such as vaccination, is present. In animal
studies, a suppression of the activated immune system by SRI*s has already been
described in several models of auto-immune diseases6-9.

In this study, we aim to assess the immunological response to hepatitis B
vaccination in OCD patients that are treated with high doses of SRI*s (60 mg/d
paroxetine). Hepatitis B vaccination has only been added to the national
vaccination programme in the Netherlands starting from 1 August 2011.
Therefore, the majority of the adult Dutch population did not receive
vaccination to hepatitis B during childhood. Although the patients that will be
included in this study are not at elevated risk for hepatitis B infection,
vaccination in these patients is considered favourable given the recent changes
in hepatitis B vaccination policy.

The immunological response in SRI-treated OCD patients will be compared to the
one in OCD patients not taking any medication. Healthy controls are not
considered a suitable reference since the immune function in healthy controls
might differ from the immune function in OCD patients. Indeed, alterations in
cytokine levels and NK cell activity have been reported in OCD patients.10

The results of this study might have important implications for both
psychiatric and immunological fields of medicine. Indeed, if SRI*s interfere
with the efficient mounting of an immune response to hepatitis B vaccination
and potentially other vaccines, adequate measures should be taken when
vaccinating patients treated with (high doses of) SRI*s. Follow-up of
serological parameters and cellular immune responses after vaccination would
then become indispensable and adjustment of vaccine doses or temporary
discontinuation of SRI-therapy should be considered.

The main objective of this study is to
1) Determine the immunological response to hepatitis B vaccination in OCD
patients that are treated with 60 mg/d paroxetine and
2) Compare this response to the immunological response to hepatitis B
vaccination in non-treated control OCD patients.

This study is an open, parallel group pilot study consisting of two groups of
patients: the first group consists of ten OCD patients treated with 60 mg/d
paroxetine. The second group consists of ten OCD patients that are not treated
with SRI*s. Healthy controls are not considered a suitable reference since the
immune function in healthy controls might differ from the immune function in
OCD patients. Thus, the underlying condition might bias the results if
comparison was made to healthy controls. No changes in pharmacological
treatment will be introduced during this study. OCD patients that are being
treated with 60 mg/d paroxetine and meet the inclusion criteria will be asked
to participate in the study and will be assigned to group 1 after written
informed consent has been obtained. OCD patients not currently taking any
serotonergic medication that meet the inclusion criteria and give informed
consent will be assigned to group 2.

Many factors affecting the immunological response after hepatitis B vaccination
have been described.11 The most important amongst them are age, sex and body
mass index (BMI). Since the present study is aiming to estimate the difference
in immunological response between OCD patients treated with 60 mg/d paroxetine
and non-treated control OCD patients in a very small cohort, these confounding
factors will be taken in consideration as much as possible at the time of
inclusion. Very narrow inclusion criteria will be used, in order to exclude the
possibility that these factors are influencing the immunological response to
hepatitis B vaccination.

A full vaccination with Hepatitis B vaccine (Engerix-B) will be performed in
all patients, i.e. three doses at months 0, 1 and 6. The immunological response
will be determined at three timepoints: prior to administration of the first
dose (month 0), prior to administration of the second dose (month 1) and 1
month after administration of the third dose (month 7). 33 ml of venous blood
will be taken at each timepoint.

Patients will be recruited from the department of psychiatry, AMC. Patients
that were previously treated at the department of psychiatry, AMC will be
invited for participation in the study by letters.

A full vaccination with Hepatitis B vaccine (Engerix-B) will be performed in
all patients, i.e. three doses at months 0, 1 and 6. The immunological response
will be determined at three timepoints: prior to administration of the first
dose (month 0), prior to administration of the second dose (month 1) and 1
month after administration of the third dose (month 7). 33 ml of venous blood
will be taken at each timepoint.

Participation in this study brings only a limited potential risk to the
patients. A registered vaccine will be administered, and blood samples (33 ml)
will be taken at three timepoints. In total, four consultations are planned for
each patient. These consultations will be scheduled as much as possible
simultaneously with the consultations that patients undergo as part of their
regular treatment, so that the burden for the patient in relation to invested
time and transport costs is kept low.