Dermatologic Clinics
Volume 23 • Number 4 • October 2005
Copyright © 2005 W. B. Saunders Company
Psychopharmacologic Therapies in Dermatology: An
Update
Chai Sue Lee, MD a
John Koo, MD b, *
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a Department of Dermatology, University of California Davis Medical Center,
Sacramento, California, USA
b Department of Dermatology, University of California San Francisco Medical
Center, San Francisco, California, USA
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* Corresponding author. University of California at San Francisco Psoriasis and
Skin Treatment Center, 515 Spruce Street, San Francisco, CA 94118
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Many patients who have skin disorders have associated psychosocial issues.
Psychotropic agents with improved side-effect profiles are available to allow
physicians who are not psychiatrists to manage patients who have psychiatric
conditions with agents that are effective, simple to administer, and generally
well tolerated. Dermatologists who wish to help their patients who have
psychodermatologic conditions can enhance their armamentarium by becoming
familiar with the use of a few selected psychotropic agents. This article
reviews the current status and future directions of psychopharmacology for the
major types of psychopathologies encountered in dermatology practice.
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Many patients who have skin disorders have psychologic or psychosocial issues
associated with their skin disorder. This can present in many different ways.
Sometimes, the underlying psychopathology of the skin manifestation is difficult
to ignore, such as delusions of parasitosis or neurotic excoriation. In other
patients, psychologic factors, such as emotional stress, can exacerbate real
skin disorders, such as acne or eczema. Also, some patients develop psychologic
problems, such as depression, as a result of their skin disorders.
The psychotropic agents now available to physicians who are treating patients
with psychiatric conditions are effective, simple to administer, have mild side
effects, and generally well-tolerated. Dermatologists who wish to help their
patients with psychodermatologic conditions can enhance their therapeutic
armamentarium by becoming familiar with the use of a few selected psychotropic
agents.
Although nonpharmacologic interventions can be effective adjunctive treatments
for patients who have psychodermatologic conditions, most dermatologists have
neither the training nor the time for nonpharmacologic treatments. For those
interested in learning about nonpharmacologic treatments, such as biofeedback
therapy, relaxation training, hypnosis, and psychotherapy, see Fried and
colleagues [1].
This article reviews two clinically useful ways to classify psychodermatologic
cases, which are discussed extensively in the literature [2], [3]. These two
classification systems can help clinicians understand what they are dealing with
and with choosing the best psychotropic agent for each patient. The current
status and future directions of psychopharmacology for the major types of
psychopathologic conditions encountered in a dermatology practice are discussed.
The intent is not to be exhaustive but to update and highlight some of the key
issues that may aid clinicians in the choice of a psychotropic agent for
particular patients and provide basic details on how to administer such agents.
CLASSIFICATION OF PSYCHODERMATOLOGIC DISORDERS
Most psychodermatologic conditions can be classified into five categories: (1)
psychophysiologic disorders, (2) primary psychiatric disorders, (3) secondary
psychiatric disorders, (4) cutaneous sensory disorders, and (5) purely
dermatologic (ie, nonpsychiatric) cases, for which psychotropic agents are used.
“Psychophysiologic disorders” is a term used to describe psychodermatologic
cases in which real skin disorders are exacerbated by psychologic factors, such
as emotional stress. There are many examples of psychophysiologic conditions in
dermatology, such as acne, psoriasis, atopic dermatitis, and dyshidrosis. For
each psychophysiologic condition, there are two types of patients: stress
responders and stress nonresponders. Stress responders are those who experience
exacerbation of their skin conditions from stress, and stress nonresponders are
those for whom their emotional states seem to have nothing to do with the
natural course of their skin diseases.
Primary psychiatric disorders refer to cases in which patients have no real skin
disease but present instead with serious psychopathology. All of the skin
manifestations are self-induced. This category includes conditions such as
delusions of parasitosis, neurotic excoriations, factitial dermatitis, and
trichotillomania. These conditions often are seen by dermatologists as the
prototypes of psychodermatologic disorders because they are more blatantly
psychogenic even though there are fewer of these patients than psychophysiologic
patients.
Secondary psychiatric disorders are those in which the patients develop
emotional problems, such as depression, as a result of having a skin disorder,
usually as a consequence of disfigurement from the skin disorder. For certain
conditions, such as vitiligo or alopecia areata, the psychosocial impact of the
skin disease is the primary difficulty experienced by the patient, because these
conditions generally are not life threatening or symptomatic.
Cutaneous sensory disorders refers to conditions in which patients have
unpleasant sensations on the skin, such as itching, burning, stinging, crawling,
or biting, with no apparent organic etiology; a psychiatric diagnosis may or may
not be present.
The last category of psychodermatologic conditions involves clinical situations
where psychotropic medications are more efficacious in treating certain bona
fide skin conditions than traditional therapeutic agents used in dermatology.
For example, the antidepressant, doxepin, is a more powerful antipruritic agent
than most of the traditional antihistamines, such as diphenhydramine (Benadryl)
or hydroxyzine (Atarax).
The second way to classify psychodermatologic cases is by the nature of the
underlying psychopathology. This helps guide the selection of an appropriate
psychotropic agent for each psychodermatologic case. Most psychodermatologic
cases fall into four psychiatric diagnoses: depression, obsessive-compulsive
disorder, anxiety, and delusional disorder. For example, if the underlying
psychopathology involves depression, the treatment is an antidepressant. It does
not matter if patients present with a primary psychiatric disorder, such as
neurotic excoriations resulting from depression; a psychophysiologic disorder,
such as psoriasis exacerbated by depression; or secondary depression resulting
from disfigurement; as long as the underlying psychopathology is depression, an
antidepressant is the most appropriate choice of treatment.
The determination of the category of psychodermatologic disorders and the
decision about the underlying psychiatric diagnosis are made independent of each
other. Any one of the four psychopathologies—depression, obsessive-compulsive
disorder, anxiety, and delusional disorder—can be found in any one of the
different categories of psychodermatologic disorders.
TREATMENT OF DEPRESSION
Depression frequently is encountered in dermatology practices. Patients report
depressed mood or anhedonia (ie, inability to feel pleasure). Feelings of
worthlessness, hopelessness, and excessive guilt are common. Patients also may
report somatic symptoms, such as loss of appetite, weight loss, sleep
disturbance, decreased energy, and difficulty concentrating. Preoccupation with
physical health may occur. The symptoms may cause significant social or
occupational dysfunction, significant subjective distress, or impairment in
functioning.
Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for
depression. Probably the only tricyclic antidepressant (TCA) worth considering
as a possible first-line antidepressant in dermatology is doxepin because of its
combined antipruritic, antihistaminic, and antidepressant effects. There also
are two antidepressants with different mechanisms of action other than SSRIs
that are worth keeping in mind when treating psychodermatologic patients who
have depression: venlafaxine (Effexor) and bupropion (Wellbutrin). Nefazodone
(Serzone) recently was removed from the market because of cases of hepatic
toxicity.
SELECTIVE SEROTONIN REUPTAKE INHIBITORS
SSRIs are the most widely prescribed class of antidepressants. They also are the
first-line treatment for obsessive-compulsive disorder. The SSRIs include
paroxetine (Paxil), sertraline (Zoloft), citalopram (Celexa), escitalopram
(Lexapro) and fluoxetine (Prozac). Fluvoxamine (Luvox) is also an SSRI. It is
not commonly used, however, to treat depression, because it is associated with
many drug interactions with cytochrome P-450 metabolized medications, and the
other SSRIs are just as effective.
The side-effect profiles of SSRIs are more alike than different given their
similar mechanisms of action. Gastrointestinal effects, such as nausea and
diarrhea, are the most common side effects. Giving the medication with food
often alleviates the nausea. Nausea usually improves after several days.
Insomnia may occur with any of the SSRIs, but fluoxetine tends to be more
activating and is more likely to produce anxiety and insomnia than the other
SSRIs. SSRIs should be given in the morning if insomnia occurs. Sedation is more
likely to occur with paroxetine. If sedation occurs, the medication should be
given at bedtime. SSRIs can be associated with sexual dysfunction. Most SSRI
studies reveal an incidence of approximately 40% for sexual difficulties, most
commonly involving difficulties with orgasm [4]. When sexual side effects occur,
switching to another class of antidepressant that causes less sexual
dysfunction, such as bupropion, is recommended.
The dosing guidelines of SSRIs are listed in Table 1. Like other antidepressant
treatments, full clinical response to SSRIs is gradual. The onset of response to
SSRIs usually begins approximately 2 to 3 weeks after the optimal therapeutic
dosage is reached, and 4 to 6 weeks are required before the full therapeutic
effect is apparent. There is no linear relationship between SSRI dose and
response. For partial responders, however, the dosage may be increased to
maximize therapeutic effect. The lack of response to one SSRI or inability to
tolerate one SSRI is not predictive of the same reaction to another SSRI.
Patients showing no improvement after 6 weeks of SSRI treatment at the usual
effective dosage should switch to another SSRI or to another class of
antidepressant, such as venlafaxine or bupropion.
Table 1 . Dosing guidelines for selective serotonin reuptake inhibitor Generic
name Trade name Standard dosage range
Paroxetine Paxil Start 20 mg every am, max 50 mg/d
Sertraline Zoloft 50 mg every day, max 200 mg/d
Citalopram Celexa Start 20 mg every day, max 40 mg/d
Escitalopram Lexapro Start 10 mg every day, max 20 mg/d
Fluoxetine Prozac Start 20 mg every am, max 80 mg/d
On discontinuation, some patients may experience dizziness, lethargy, nausea,
irritability, and headaches. These symptoms can be prevented by tapering the
medication slowly over several weeks when discontinuing the drug.
OTHER NOTEWORTHY ANTIDEPRESSANTS
Although SSRIs currently are the most frequently prescribed antidepressants,
they are effective in only 60%–70% of patients. Furthermore, some patients may
be unable to tolerate the side effects of SSRIs. Two antidepressants provide
important alternatives to SSRIs in the pharmacologic therapy of depression:
venlafaxine and bupropion. Although these antidepressants share with SSRIs a
similar level of efficacy and time to onset of action, they have different
mechanisms of action and side-effect profiles.
VENLAFAXINE
Venlafaxine is a novel antidepressant that is believed to act by selectively
inhibiting serotonin and norepinephrine reuptake with little effect on other
neurotransmitter systems [5]. Several clinical studies provide evidence that
venlafaxine may offer advantages over conventional therapy in terms of an
increased number of responders and improved long-term efficacy [6], [7]. In
addition, venlafaxine has an anxiolytic effect and may be useful particularly in
patients who have mixed symptoms of depression and anxiety [8], [9], [10], [11].
A prospective, 12-week, randomized, double blind, placebo-controlled study finds
that once-daily venlafaxine extended-release (XR) preparation is more effective
than fluoxetine in patients who have major depression and concomitant anxiety
[8]. Venlafaxine XR also is shown to be effective for the treatment of anxiety
alone [12], [13], [14].
Venlafaxine comes in two formulations: immediate release and XR. Immediate
release treatment begins with 75 mg per day in two divided doses with food. The
dosage can be increased by 75 mg per day after several weeks of treatment for
partial responders. The usual effective dosage is 75–225 mg per day on a
twice-daily schedule. XR treatment begins with 37.5–75 mg per day with food. The
maximum recommended dose is 225 mg per day.
Venlafaxine has a relatively benign side-effect profile. The most common side
effects are insomnia and nervousness. Nausea, sedation, fatigue, sweating,
dizziness, headache, loss of appetite, constipation, and dry mouth also are
common. Like SSRIs, venlafaxine may cause sexual dysfunctions in approximately
10% of patients after several weeks of treatment. Venlafaxine is reported to
cause hypertension in approximately 3% of patients and seems to be dose related.
Blood pressure should be monitored during venlafaxine therapy. Although
venlafaxine-induced hypertension may be managed with standard antihypertensives,
the authors recommend switching to another class of antidepressants if
hypertension develops.
Venlafaxine can produce dizziness, insomnia, dry mouth, nausea, nervousness, and
sweating with abrupt discontinuation. Consequently, it should be tapered slowly
over several weeks.
BUPROPION
Bupropion differs from all other types of antidepressants in its chemical
structure and in its proposed mechanism of action. Bupropion is a relatively
weak inhibitor of dopamine reuptake with modest effects on norepinephrine
reuptake and no effect on serotonin reuptake [15]. Bupropion is shown as
effective as SSRIs in the treatment of depression but causes few sexual side
effects [16], [17]. In addition, bupropion may be considered for depressed
patients who have sleep difficulties, because bupropion promotes normal sleep
pattern [18], [19].
Bupropion comes in two formulations: immediate and sustained release. For
immediate release, treatment begins at 200 mg per day, given as 100 mg twice
daily. After 4–7 days, the dosage may be increased to 300 mg per day, given as
100 mg three times per day. The usual effective dosage is 200 to 300 mg per day,
divided in two to three equal daily doses. For sustained release, treatment
begins with 150 mg per day, given as a single daily dose in the morning. After
4–7 days, the dosage may be increased to 300 mg per day, given as 150 mg twice
daily if the 150 mg initial dose is adequately tolerated. The usual adult target
dosage is 300 mg per day given as 150 mg twice daily.
In general, bupropion is a well-tolerated medication. The most common side
effects are insomnia, agitation, headache, constipation, dry mouth, nausea, and
tremor. A rare but serious adverse effect of bupropion is seizure induction. The
incidence of seizures in patients receiving buproprion increases above the
therapeutic dosages of 300 mg per day [20]. Bupropion should not be used in
patients who have a history of seizure or who have conditions, such as bulimia,
that potentially may lower the seizure threshold. This medication should be
avoided in drug or alcohol abusers.
DOXEPIN
The TCA doxepin (Sinequan) probably is the ideal agent for the treatment of
depressed patients who have neurotic excoriations. In addition to its
antidepressant effect, doxepin has strong antipruritic effect because it is a
powerful H1 antihistamine. To stop the excoriating behavior, it is important to
treat patients' depression and put an end to the itch/scratch cycle. Moreover,
the majority of depressed patients who present with excoriations seem to be
suffering from an agitated depression in which the patients paradoxically become
more restless, angry, and argumentative when depressed. For these patients, the
most common side effect of doxepin, sedation, can be therapeutic.
The usual starting dosage of doxepin for depression is 25 mg per day at bedtime.
The dosage can be titrated with 10–25 mg increments every 5–7 days, as
tolerated, up to the usual therapeutic range for depression, which is anywhere
from 75 to 300 mg per day. In general, it takes at least 2 weeks after the
therapeutic dosage is reached before the antidepressant effect is observed. Some
patients may require 6–8 weeks of treatment before responding. The other
therapeutic effects of doxepin, however, such as the antipruritic effect,
effects in calming patients down, and improving insomnia, generally occur
immediately. If patients show no response, despite taking a large dose of
doxepin for several weeks, it may be helpful to check a serum doxepin level to
see if it is within the therapeutic range for depression.
The most common side effect of doxepin is sedation. The sedative side effect
usually can be avoided by taking it at bedtime. More persistent sedation may
require lowering the dosage or changing the time of administration of doxepin.
For example, if patients complain of difficulty waking up in the morning, this
usually can be overcome by taking doxepin earlier than bedtime or by dividing
the dose so that patients take some of the dose when they get home and the rest
at least 1–2 hours before bedtime. This way, patients are less likely to
experience excessively high peak serum level and the resultant sedation the next
morning. The other side effects of doxepin are similar to those of other older
TCAs, including cardiac conduction disturbances, weight gain, orthostatic
hypotension, and anticholinergic side effects, such as dry mouth, blurry vision,
constipation, and urinary retention. TCAs may slow cardiac conduction, resulting
in intraventricular conduction delay, prolongation of the QT interval, and
atrioventricular block. Therefore, TCAs are contraindicated in patients who have
preexisting conduction defects, arrhythmias, or recent myocardial infarction. A
pretreatment EKG is recommended to rule out the presence of prolonged QT in
older patients or any patients who have a history of cardiac conduction
disturbance. In addition, an EKG should be repeated to rule out dysrhythmia if
doxepin is used in dosages of 100 mg per day or higher. Doxepin also should be
used with caution in patients who have a history of seizure disorder or
manic-depressive disorder because it can lower the seizure threshold and
precipitate a manic episode.
Abrupt discontinuation of TCAs may lead to transient dizziness, nausea,
headache, diaphoresis, malaise, insomnia, and REM rebound, with uncomfortably
vivid dreams. Consequently, they should be tapered gradually over several weeks
after prolonged treatment with TCAs. Slow taper also decreases the likelihood of
relapse of depressive symptoms.
TREATMENT OF OBSESSIVE-COMPULSIVE TENDENCY
An obsession is a repugnant thought that intrudes repetitively into the thought
process of a patient. Compulsion refers to repetitious, stereotyped behavior
that is difficult for patients to suppress. The diagnosis of
obsessive-compulsive tendency may be justified if either the obsession or the
compulsion is of sufficient intensity to interfere with a patient's lifestyle or
cause significant subjective distress. Some patients may present only with
obsession, whereas others present only with compulsive behaviors. For example,
some patients may obsess about the “unsightly greasiness” of their face without
engaging in any special activity to try to correct the greasy complexion,
whereas other patients may present with an irresistible compulsion to pick their
acne without having any special thought process associated with their
compulsion.
An obsession can be mistaken for a delusion, because in both cases patients
present with a mental preoccupation involving an overvalued idea. The key
distinction between obsession and delusion is the presence or absence of insight
on the part of the patient. Most adult patients who have obsessive-compulsive
tendencies usually recognize and acknowledge the excessive, unreasonable, and
destructive nature of their obsessions and compulsions, but are unable to stop
obsessive thoughts or their compulsive behaviors. In contrast, delusional
patients truly believe in the validity of their delusional thoughts. Frequently,
patients who have obsessive-compulsive tendencies are apologetic for their
thoughts or behaviors. For example, a patient who has acne excoriée may say, “I
know I am not supposed to be doing this, and I know that if I keep picking on my
acne I might really scar myself, but I can't stop picking because when I try to
stop, I feel this tremendous urge to pick my acne.” The presence of such a
compulsive urge that intensifies until patients finally give in and engage in
the compulsive activity—despite the presence of good insight—helps differentiate
obsessive-compulsive tendency from delusional disorder. Unfortunately, not all
patients are so typical in their clinical presentation, and, in some cases,
obsessive-compulsive tendency and delusion can be difficult to differentiate.
There are many manifestations of obsessive-compulsive tendencies in dermatology.
Skin findings in obsessive-compulsive tendencies include eczematous eruptions
related to excessive washing, hair loss related to trichotillomania or
compulsive hair pulling, and excoriations related to neurodermatitis or
compulsive skin picking. Obsessive-compulsive tendencies usually have a chronic
course, and few patients achieve true remission [21]. Although symptoms may wax
and wane over time, the disorder rarely resolves spontaneously without
appropriate treatment [22], [23].
SSRIs are the first-line treatment for obsessive-compulsive disorder (see
previous discussion of depression.) Obsessive-compulsive symptoms often require
higher doses of an SSRI and take longer to respond then when treating
depression. In obsessive-compulsive disorder, initial response to a SSRI can
take 4–8 weeks, and maximal response may take as long as 20 weeks. Complete
remission is unusual. A 10- to 12-week trial with a SSRI at therapeutic dosage
is the minimum necessary to confirm true failure to respond. A failure to
respond to one SSRI does not predict failure to respond to another [24]. For
nonresponders, a 10-week trial of a SSRI followed by a switch to another SSRI is
the recommended practice by the authors if a psychiatric referral is not
feasible. Therapy should be continued for at least 6 months to 1 year once a
therapeutic response is achieved [22]. Medications should be tapered slowly
during discontinuation and should be restarted if symptoms reappear.
No matter which medication is used, patients must be told that these medications
are not magic bullets. They can be helpful in overcoming obsessive thoughts or
compulsive behaviors, but they are no substitute for the patients' own
motivation to stop destructive behaviors. Therefore, patients should be
encouraged to keep up their own efforts and vigilance in controlling their
compulsive behaviors while they undergo treatment with anti–obsessive-compulsive
medications.
TREATMENT OF ANXIETY
Patients who have anxiety disorder report excessive anxiety and stress, which
may revolve around valid concerns about money, jobs, marriage, health, and so
forth. Patients also may report restlessness or feeling on edge, difficulty
concentrating or mind going blank, and irritability. In addition to subjective
feelings, patients who have excessive anxiety and stress may experience
physiologic manifestations of anxiety that may include palpitations,
lightheadedness, dizziness, sweaty palms, difficulty breathing, trembling,
muscle aches and soreness, and sleep disturbance. The subjective anxiety or the
associated physical symptoms can cause significant distress and impairment in
functioning.
Psychodermatologic cases involving anxiety often can be divided into two groups:
acute and chronic anxiety. The acute and time-limited episode of anxiety usually
involves a specific situational stress, such as increasing demand at work,
interpersonal difficulty, or a financial crisis. The situational stress can
exacerbate a stress-responder's skin disorder. The use of an anxiolytic agent
may be indicated for a few weeks to avert a flare of the skin condition and
improve mental stability until patients recover from the crisis, especially if
nonpharmacologic approaches are either not feasible or not adequate to control
the anxiety. The decision as to the treatment of choice for psychodermatologic
cases involving anxiety should take into account if the anxiety is acute (short
term) or chronic.
BENZODIAZEPINES
Benzodiazepines are useful especially in the management of acute situational
anxiety. Unlike patients who have chronic anxiety, many of these patients who
have acute situational anxiety have adequate coping skills and usually recover
from the crisis after a few weeks. This period of stress can be long enough,
however, to exacerbate their skin disorder. Benzodiazepines take effect
immediately and almost always can relieve anxiety if given in adequate doses.
For acute anxiety in dermatology patients who have not tried benzodiazepines
before, treatment can begin with alprazolam (Xanax), half a 0.25-mg tablet up to
four times per day, on an as-needed basis.
Benzodiazepines generally are well tolerated. For short-term use (≤6 weeks), the
main side effect is sedation, but usually this subsides after several days of
treatment or can be controlled by dosage adjustment. It is helpful for patients
to take an initial dose at home in the evening to see how it affects them when
treatment is initiated, especially with regard to the possible sedative effect.
Patients should be cautioned against driving after taking benzodiazepines.
Because of the potential risk of addiction with long-term use, physicians should
try to limit the duration of treatment with benzodiazepines to no more than 3 to
4 weeks. In many cases, the situational stress resolves during the treatment
period.
BUSPIRONE
Buspirone (Buspar) is preferred for the treatment of chronic anxiety because it
is an antianxiety medication that is nonsedating and does not cause dependency.
Its main disadvantage, however, is its delayed onset of action and, therefore,
buspirone cannot be used on an as-needed basis. Buspirone must be administered
for at least 2 weeks before a significant therapeutic effect occurs. Because of
the slow onset of action, this agent is not appropriate for the treatment of
acute situational stress, because the therapeutic effect may not become evident
until after the stressful event has resolved.
The starting dosage is 15 mg per day given as 7.5 mg twice daily and increased
to 15 mg twice daily after 1 week. The maximum dosage is 60 mg per day. Most
patients respond to dosages between 15 and 30 mg per day. The 15- and 30-mg
tablets are scored to be bisected or trisected easily.
Buspirone generally is well tolerated. Most patients experience no adverse
effects. The most common side effects are nausea, headache, dizziness, and
fatigue. Patients treated previously with benzodiazepines or who have a history
of substance abuse seem to have a decreased response to buspirone, because it
lacks the euphoria, sedation, and immediate action these patients may have come
to expect with anxiety relief.
ANTIDEPRESSANTS
Antidepressants, such as paroxetine (20–50 mg per day), low-dose doxepin (≤50 mg
per day), and venlafaxine XR (75 and 150 mg per day), also are shown to be
useful for the treatment of chronic anxiety (see earlier discussion) [12], [13],
[14], [25], [26].
TREATMENT OF DELUSIONAL DISORDER
The delusional disorders encountered most often by a dermatologist are
monosymptomatic hypochondriacal psychosis (MHP). Patients who have MHP are
characterized by the presence of an “encapsulated” delusional ideation that
revolves around one particular hypochondriacal concern. This can be associated
with hallucinatory experiences that are compatible with the delusion. For
example, the most common MHP seen by dermatologists is delusions of parasitosis.
Many patients who have delusions of parasitosis experience cutaneous sensations
of crawling, biting, and stinging along with their delusions. MHP is different
from schizophrenia in that individuals who have schizophrenia have other
psychologic disturbances in addition to delusions.
PIMOZIDE
The most commonly used pharmacologic treatment for delusions of parasitosis is
the antipsychotic medication pimozide. Careful titration of pimozide dosage is
the key to safe use of this medication. Because of the possibility of
extrapyramidal adverse effects, such as stiffness and restlessness, patients
should begin treatment at a low initial dosage of 1 mg daily, which can be
increased by 1 mg increments every 4–7 days until either optimal clinical
response is reached or patients are taking 4–6 mg per day. Even though dosages
as high as 10 mg per day are used in dermatologic settings, the authors
generally do not recommend going beyond 4–6 mg per day because the risk of side
effects increases.
Once the delusions of parasitosis no longer interfere significantly with
patients' capacity to work or enjoy life, this clinically effective dosage is
maintained for at least 1 month. The dosage of pimozide can be decreased
gradually by 1 mg as quickly as every 1–2 weeks until either the minimum
effective dosage is determined or patients successfully are tapered off pimozide
altogether. Although some patients who have delusions of parasitosis can be
tapered off pimozide successfully after 2–4 months, 5–6 months of treatment is a
more reasonable expectation. If delusions of parasitosis recur after pimozide is
discontinued, patients can be restarted on pimozide in a time-limited fashion.
Long-term use of pimozide is best avoided to minimize the risk of tardive
dyskinesia developing in these patients. This side effect is characterized by
abnormal involuntary rhythmic movements of the face, mouth, tongue, or jaw,
which sometimes may be accompanied by involuntary movements of the trunk and
extremities. Tardive dyskinesia is the most worrisome adverse effect of
pimozide, because it may be irreversible. No cases of pimozide use for MHP
causing tardive dyskinesia are reported except for one questionable case.
Lindskov reports a patient who had delusions of parasitosis and a “slight
twitching of her lips” which “has been present since treatment” [27]. Although
the original investigators never labeled this explicitly as tardive dyskinesia,
another investigator later interpreted this case as “tardive dyskinesia” [28].
The most common side effects of pimozide are the acute forms of extrapyramidal
side effects manifested by stiffness and a feeling of inner restlessness called
akathisia. Akathisia is manifested outwardly by difficulty remaining still and
fidgeting or pacing. Even though only a minority of patients treated with
pimozide experience extrapyramidal side effects, it is advisable for clinicians
to explain the possibility of developing such adverse effects before starting
pimozide and to give a prescription for either benztropine 1–2 mg up to four
times per day or diphenhydramine 25 mg up to four times per day in case patients
begin to have symptoms of extrapyramidal side effects. The advantage of
benztropine over diphenhydramine is that the former agent is not sedating.
Because some patients may have considerable ambivalence about taking pimozide,
if they develop extrapyramidal side effects and do not have the means to control
them right away, they may decide never to take pimozide. Such a decision can be
tragic, because without proper treatment, delusions of parasitosis can last for
decades with virtual incapacitation of many of these patients. As long as the
extrapyramidal side effects can be controlled with one of the two medications
described above, patients can continue with treatment with pimozide and even
increase the dose until the optimal dosage is reached.
There are reports of sudden death, presumably cardiac related, in patients who
had chronic schizophrenia and who were treated with high-dose pimozide above 10
mg per day [29]. Pimozide theoretically can cause arrhythmias by prolonging the
QT interval. To date, the authors have not seen any EKG change from low-dose
pimozide used to treat MHP. For those who have a history of cardiac conduction
abnormalities or arrhythmia, a pre- and posttreatment EKG should be checked. For
those who are young and healthy and have no history of cardiac arrhythmias, it
is controversial whether or not an EKG is warranted if the dosage is less than
10 mg per day [29].
ATYPICAL ANTIPSYCHOTICS
Three atypical antipsychotics—risperidone (Risperdal), olanzapine (Zyprexa), and
quetiapine (Seroquel)—are the most frequently prescribed medications for the
treatment of psychosis. These newer antipsychotic agents are dopamine and
serotonin receptor antagonists. Atypical antipsychotics have greatly reduced the
incidence of extrapyramidal side effects and tardive dyskinesia because they are
more selective in binding to the receptors that are believed related to
antipsychotic effects but not to the other receptors that are related to side
effects [30], [31], [32], [33]. These atypical antipsychotics, with a much safer
side-effect profile, may prove useful for the treatment of MHP. The optimal
dosage range for MHP is not established for any of these agents. Studies
comparing pimozide with the atypical antipsychotics in the treatment of
delusions of parasitosis have not yet been done.
Atypical antipsychotics should be used with caution in patients who have a
history of seizures or with conditions, such as Alzheimer's disease, that
potentially lower the seizure threshold. During premarketing testing, seizures
occurred in 22 (0.9%) of 2500 olanzapine-treated patients, 18 (0.8%) of 2387
quetiapine-treated patients, and 9 (0.3%) of 2607 risperidone-treated patients
[34].
RISPERIDONE
Risperidone treatment for nondermatologic psychoses begins with 1 mg twice
daily, and the dosage may be increased slowly every 5–7 days to the usual
effective dosage of 4–6 mg per day on a twice-daily schedule. After titration,
patients may take the entire dose at bedtime. Because the optimal dosage for MHP
is not established, the authors generally recommend an even more cautious 1-mg
once-daily starting dosage. The most common side effects are anxiety, dizziness,
and rhinitis. Dose-related side effects include sedation, fatigue, and
accommodation disturbance. Risperidone is known to prolong the QT interval and
should be used with caution in patients who have abnormal baseline QT intervals
or those taking other medications that can prolong the QT interval (eg,
antiarrhythmics, such as quinidine or procainamide) [30], [31], [32], [35]. As
the only available atypical antipsychotic with minimal anticholinergic effects
(eg, dry mouth, blurry vision, urinary retention, and constipation), risperidone
may be considered the agent of choice for the elderly [36], [37]. Risperidone is
reported effective in the treatment of delusions of parasitosis [38].
OLANZAPINE
Olanzapine treatment for nondermatologic psychoses begins with 5–10 mg per day.
The usual effective dosage is 10–15 mg per day. Once again, because the optimal
dosage for MHP is not established, the authors recommend a lower starting dosage
for dermatologic use. The most common side effects are sedation, anticholinergic
effects, and weight gain.
QUETIAPINE
Quetiapine treatment for nondermatologic psychoses starts with 25 mg two times
per day. The usual effective dosage is 150–750 mg per day. Again, because the
optimal dosage for MHP is not established, the authors recommend a lower
starting dosage for dermatologic use. The most common side effects are mild
somnolence and mild anticholinergic effects. Quetiapine is associated more often
with orthostatic hypotension than the other atypical antipsychotics but usually
is manageable with careful dose adjustment, and patients frequently become
partially or fully tolerant to it [39].
USE OF PSYCHOTROPIC MEDICATIONS FOR TREATING PURELY DERMATOLOGIC CONDITIONS
Certain psychotropic medications are known to be useful in treating purely
dermatologic conditions. The class of medications with the most well-documented
analgesic effect is the older tertiary TCAs, such as doxepin and amitriptyline
[40], [41], [42], [43], [44], [45]. If pruritus is the primary problem, doxepin
is the preferred agent. Alternatively, if various manifestations of pain, such
as burning, stinging, biting, or chafing, are the primary sensations,
amitriptyline is the preferred starting agent.
DOXEPIN FOR PRURITUS AND OTHER DERMATOLOGIC CONDITIONS
Doxepin frequently is used to treat pruritus when more conventional antipruritic
agents, such as diphenhydramine or hydroxyzine, are inadequate. There are
several advantages of using doxepin for the control of pruritus compared with
the conventional antipruritic agents. First, doxepin has a higher affinity for
the histamine receptors than the traditional antihistamines and, therefore,
exert a more powerful antipruritic effect. For example, the affinity of doxepin
for H1 receptor in vitro is approximately 56 times that of hydroxyzine and 775
times that of diphenhydramine [46]. Second, the therapeutic effect of doxepin is
much longer than either of these H1-antihistamine medications. Because of its
long half-life, doxepin taken once daily, usually at bedtime, is adequate to
provide therapeutic benefit up to 24 hours. Therefore, patients who have
severely pruritic conditions, such as atopic dermatitis, who complain of waking
up in the middle of the night even though they are taking hydroxyzine or
diphenhydramine before bedtime, usually find that when they switch to doxepin,
they can sleep throughout the night. Third, doxepin normalizes sleep curves.
When patients spend more time in a deeper state of sleep, the amount of
nighttime excoriation often diminishes dramatically. Doxepin also can be helpful
in treating patients who have chronic urticaria or other disorders mediated by
histamines who have failed treatment with traditional antihistamines [47], [48].
The dosing guideline for doxepin is discussed previously in the treatment of
depression section. There are no good data regarding the optimal dosage for the
treatment of conditions, such as pruritus or urticaria. A wide range in dosing
is possible depending on individual patients. For example, the dosage of doxepin
adequate for control of pruritus may range from as little as less than 10 mg at
bedtime (often using doxepin liquid preparation, which is 10 mg/mL) to as much
as the maximum dosage for the treatment of depression 300 mg at bedtime.
AMITRIPTYLINE
For various manifestations of pain sensations, such as burning, stinging,
biting, or chafing, amitriptyline is the preferred agent over doxepin because of
better documentation of its efficacy as an analgesic. When TCAs are used as
analgesics, the dosage required tends to be less than the dosage required for
its antidepressant effect. Patients can be started at 25 mg at bedtime and
titrated to the maximally effective dosage. For use as an analgesic, a dosage of
50 mg per day or less usually suffices. Side effects of amitriptyline are the
same as for doxepin and include sedative, cardiac, anticholinergic, and
α-adrenergic side effects, including orthostatic hypotension, which can be
problematic particularly in elderly patients. If patients cannot tolerate these
agents, other TCAs, such as imipramine or desipramine may be used [49]. The
dosage range for these medications is the similar to that for amitriptyline.
SUMMARY
The majority of mental illnesses, including psychodermatologic conditions,
generally are considered chronic. Psychiatric referral and consultation should
be attempted whenever feasible. Yet, for a significant proportion of patients
who refuse psychiatric referral, the judicious use of psychotropic medications
by dermatologists may provide much-needed assistance in the recovery of these
patients from psychodermatologic disorders when no other avenue of assistance
exists. Though detailed explanations regarding the use of selected old and new
psychopharmacologic agents were discussed in this article, the reader is advised
to consult standard textbooks on psychopharmacology and the Physician's Desk
Reference for a more complete description regarding the indications for the use
of these medications.
--------------------------------------------------------------------------------
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