Premenstrual Syndromes : PMS and PMDD - Rutuja :: The site ...

15
Psychotropic therapies
Meir Steiner and Claudio N Soares
INTRODUCTION
We have seen in previous chapters that the current
management of severe premenstrual syndrome (PMS)
and premenstrual dysphoric disorder (PMDD) includes
hormonal, alternative, and non-medication therapies
as well as ovarian suppression (see Chapters 14, 15,
and 17). Limited evidence supports the effectiveness of
some of these treatment strategies, particularly the complementary
and so-called ‘natural remedies’; in addition,
potential side effects and risks involving long-term
use of hormone treatments may limit their use.
Evidence from numerous open-label as well as randomized
placebo-controlled trials (RCTs) has clearly
demonstrated the efficacy of the selective serotonin
reuptake inhibitors (SSRIs) and, to a lesser degree, the
serotonin/norepinephrine reuptake inhibitors (SNRIs),
either when used continuously or intermittently. Overall,
the use of these agents has shown excellent efficacy and
minimal side effects. This chapter will summarize this
evidence and will also discuss the potential use of anxiolytics
in this population.
ANTIDEPRESSANTS
Of all the neurotransmitters studied to date, serotonin
has been identified as the most plausible candidate to
be relevant in the pathophysiology of PMS and PMDD
(see Chapter XX). It has been suggested that women with
severe PMS or PMDD are more sensitive to the premenstrual
decrease in circulating progesterone metabolites.
It has been suggested that serotonergic agents
have the potential for enhancing the production of these
metabolites and thus prevent the occurrence of premenstrual
symptoms (see Chapters 7, 10, and 12). It
should therefore come as no surprise that pharmacological
interventions have focused primarily on such
agents.
A Swedish group of researchers deserves the credit
for being the first to show that a relatively small dose
(25–50 mg) of clomipramine, a non-selective serotonin
reuptake inhibitor, was effective in reducing symptoms
of irritability and sadness in women with severe PMS. 1
Subsequent open-label as well as RCTs have all confirmed
the efficacy of clomipramine 2 as well as of the
SSRIs 3–20 and the SNRIs. 21,22 Initially most of these
trials reported on continuous daily dosing of the medication
(Table 15.1).
It soon became evident that not only do women with
severe PMS or PMDD respond to somewhat lower doses
of these antidepressants as compared with the usual
doses needed in depression or some of the anxiety disorders
but also that the onset of action was much shorter
(days rather than weeks). This observation, along with
the fact that premenstrual symptoms are generally limited
to the luteal phase of the cycle, led the same Swedish
group to initiate the first ever study of intermittent
(luteal phase only) administration of clomipramine. 23
Again, subsequent open-label as well as RCTs have
confirmed the efficacy of SSRIs 24–37 and SNRIs 38 when
administered intermittently (Table 15.2).
The form of intermittent dosing that has been evaluated
is treatment enduring for the last 2 weeks of the
menstrual cycle. With intermittent or luteal phase dosing,
treatment is initiated around the time of ovulation and
is discontinued 1 or 2 days after the onset of menstruation.
Intermittent dosing should not be confused with
symptom-onset therapy, in which treatment begins
immediately after the first appearance of symptoms. 26,36
An intermittent dosing regimen is a reasonable choice
for patients with regular menstrual cycles who are able
to adhere to the on/off dosing regimen, for patients with
no evidence of mood symptoms during the follicular phase
(i.e. patients whose symptoms persist throughout the
menstrual cycle), for patients concerned about long-term
adverse effects (e.g. sexual dysfunction), and for patients
who experience few side effects at treatment initiation.