Letters to the Editor
Depression in Multiple Sclerosis Associated With Interferon Beta-1a
(Rebif)
Dear Editor:
The lifetime risk of depression in those with multiple sclerosis
(MS) is very high, with some estimates exceeding 50% (1). In initial
trials of interferon beta-1b, there were several suicide attempts
and 1 completed suicide, compared with no suicides in the placebo
group (2). Since that time, there has been concern that interferon
treatment can cause depressive symptoms, and the product monograph
suggests that patients treated with interferon beta-1b be “informed
that depression and suicidal ideation may be a side effect of treatment”
(3). Some recent studies have not confirmed this association. The
following case suggests a causal link between interferon beta-1a
treatment of MS and major depressive disorder.
Case Report
A 42-year-old Caucasian woman diagnosed in March 2001 with clinically
definite relapsing and remitting MS was started on interferon beta-1a
therapy the same month. The Center for Epidemiological Studies Depression
Rating Scale (CES-D) score (4,5), obtained prior to initiation of
interferon beta-1a, was 4. A second rating, obtained in September
2001, was 28. The patient described a 5-month history of sustained
depressed mood, crying spells, sleep disturbance (early morning
awakening), hostility, amotivation, apathy, no libido, poor concentration
and short-term memory, and a depressed cognitive shift (that is,
feelings of hopelessness and guilt). Regarding psychiatric history,
the patient had never seen a psychiatrist or mental health professional
prior to the consultation in December 2001. However, she did acknowledge
a remote history of bulimia nervosa in her teens. Medical history
and family history were not contributory to her depression.The patient
was started on citalopram in November 2001, and 6 weeks after initiation
of the antidepressant she noticed a decrease in sadness and hostility.
Her sleep also improved. A CES-D was repeated in December 2001 and
her score was 23.
The 5 point reduction in CES-D scores was modest, but there was
a significant clinical reduction in depressive symptomatology, and
she was able to continue with interferon beta-1a treatment. It has
been shown that patients with MS who have depression often discontinue
therapy (6); this patient felt well enough to continue with her
prescribed disease-modifying therapy.
An analysis of depression data from the PRISMS clinical trial showed
no evidence of increased depressive symptomatology associated with
interferon beta 1a (the median change in CES-D score after 6 months
of treatment was 0) (7). While the PRISMS trial provides evidence
that depression must be a rare event during interferon treatment,
clinicians should maintain an index of suspicion. If significant
depressive symptoms arise, pharmacotherapeutic treatment appears
to be an option. In our case, there was a beneficial response to
selective serotonin reuptake inhibitor (SSRI) therapy (citalopram).
Recent studies have shown that prophylactic treatment with paroxetine
is an effective strategy to minimize depression induced by treatment
with interferon alfa-2b for malignant melanoma (8). It is also evident
that swift detection and treatment can reduce the impact of major
morbidity associated with MS.
References
1. Minden SL, Orav L, Reich P.
Depression in multiple sclerosis. Gen Hosp Psych 1987;9:426–34.
2. Klapper JA. Interferon beta
treatment of multiple sclerosis. Neurol 1994;44:188.
3. Canadian Pharmacists Association.
Compendium of pharmaceuticals and specialties 36th ed. Ottawa: Canadian
Pharmacists Assoc; 2001.
4. Radloff LS. The CES-D scale:
a self-report depression scale for research in the general population.
Applied Psychological Measurement 1977;1:385–401.
5. Weissman MM, Sholomskas D,
Pottenger M, Prusoff BA, Locke BZ. Assessing depressive symptoms
in five psychiatric populations: a validation study. Am J Epidemiol
1977;106:203–14.
6. Mohr DC, Goodkin DE, Likosky
W, Gatto N, Neilly LK, Griffin C and others. Therapeutic expectations
of patients with multiple sclerosis upon initiating interferon beta-1b:
relationship to adherence to treatment. Mult Scler 1996;2:222–6.
7. Patten SB, Metz LM. Interferon
beta-1a and depression in relapsing-remitting multiple sclerosis:
an analysis of depression data from the PRISMS clinical trial. Mult
Scler 2001;7:243–8.
8. Musselman DL, Lawson DH, Gumnick JF, Manatunga
AK, Penna S, Goodkin RS, and others. Paroxetine for the prevention
of depression induced by high-dose interferon alfa. N Engl J Med
2001;344:961–6.
Rupang Pandya, BSc, MD
Scott Patten, MD, FRCPC, PhD
Calgary, Alberta
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