Case 3: Volume 1, Case #5: The Sleepy Woman with Anxiety

· Review this week’s Learning Resources and reflect on the insights they provide.

· Go to the Stahl Online website and examine the case study you were assigned.

· Take the pretest for the case study.

· Review the patient intake documentation, psychiatric history, patient file, medication history, etc. As you progress through each section, formulate a list of questions that you might ask the patient if he or she were in your office.

· Based on the patient’s case history, consider other people in his or her life that you would need to speak to or get feedback from (i.e., family members, teachers, nursing home aides, etc.).

· Consider whether any additional physical exams or diagnostic testing may be necessary for the patient.

· Develop a differential diagnosis for the patient. Refer to the DSM-5 in this week’s Learning Resources for guidance.

· Review the patient’s past and current medications. Refer to Stahl’s Prescriber’s Guide and consider medications you might select for this patient.

· Review the posttest for the case study.

Note:

 For this Discussion, you are required to complete your initial post before you will be able to view and respond to your colleagues’ postings. Begin by clicking on the “Post to Discussion Question” link and then select “Create Thread” to complete your initial post. Remember, once you click on Submit, you cannot delete or edit your own posts, and you cannot post anonymously. Please check your post carefully before clicking on 

Submit

!

Post a Response to the Following:

1-Provide the Case Study number in the subject line of the Discussion.

2-List Three Questions you might ask the patient if he or she were in your office. Provide a rationale for WHY you might ask these questions.

3-Identify people in the patient’s life you would need to speak to or get feedback from to further assess the patient’s situation.

4- Include Specific Questions you might ask these people and WHY.

5-Explain what Physical Exams and Diagnostic Tests would be appropriate for the patient and HOW the results would be used.

5-List Three Differential Diagnoses for the patient.

6- Identify the ONE that you think is most likely and Explain Why.

7-List TWO Pharmacologic agents and their dosing that would be appropriate for the patient’s Sleep/Wake Therapy based on pharmacokinetics and pharmacodynamics.

8-From a mechanism of action perspective, Provide a Rationale for Why you might choose ONE agent over the other.

9-If your assigned case includes “check points” (i.e., follow-up data at week 4, 8, 12, etc.), indicate any Therapeutic Changes that you might make based on the data provided.

10-Explain “Lessons Learned” from this case study, including HOW you might apply this case to your own practice when providing care to patients with similar clinical presentations.

Read a selection of your colleagues’ responses.

47

PATIENT FILE

The Case: The sleepy woman with anxiety

The Question: How can you be anxious and narcoleptic at the same time?

The Dilemma: Finding an effective regimen for recurrent, treatment

resistant anxious depression while juggling complex treatments for sleep

disorders

Pretest Self Assessment Question (answer at the end of the case)
Which of the following are approved treatments for treatment resistant

depression?

A. Deep brain stimulation
B. Transcranial magnetic stimulation
C. Vagal nerve stimulation
D. Aripiprazole (Abilify)
E. Quetiapine (Seroquel)
F. MAO inhibitors

Patient Intake
• 44-year-old woman with a chief complaint of anxiety

Psychiatric History
• The patient had onset of anxiety and depression at about age 15, which

she began self-medicating with alcohol
• After graduating from high school, she began college and was about to

leave for study abroad when she experienced a panic attack for which
she was treated in the emergency room

• She was then hospitalized and treated for alcohol abuse at age 18,
and has remained sober ever since, although she does admit to some
possible alprazolam (Xanax) abuse in 1999 as well as one overdose
with alprazolam

• Her history also includes multiple hospitalizations for major depression
– Age 19 (approximately one year after her release from the hospital

for alcohol abuse) because she became suicidal
– Age 24 due to recurrence of depression
– Age 26 with an overdose following a divorce and recurrence of

depression
– Age 27 due to recurrence of depression
– Age 29 after two miscarriages, with a possible postpartum element

and some discontinuation of her medications at that time to try to
get pregnant

– Age 30 when she received electroconvulsive therapy (ECT): 7
sessions as an inpatient and 23 as an outpatient

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48

PATIENT FILE

• Details of medication history unclear from available information and
from patient’s memory, but has received numerous psychotropic drugs
including antidepressants, antipsychotics, and mood stabilizers, all
with poor

results

• She was much better for several years following her ECT treatment, but
had severe memory impairment

• She had a recurrence of her depression one year ago severe enough
to become totally disabled, necessitating resignation from a job as an
offi ce worker that she had enjoyed

• She continues to be disabled from depression and has a great deal
of anxiety, subjectively more disturbed by her anxiety than by her
depression

Social and Personal History
• Married since 1996 (second marriage); no children from either

marriage
• Non smoker
• Husband an architect, supportive
• Little contact with her family of origin
• Few friends or outside interests

Medical History
• Narcolepsy
• Restless legs syndrome
• Nighttime urinary incontinence possibly related to highly sedating

medications
• BMI 26
• BP 120/78
• Normal fasting glucose and triglycerides

Family History
• Grandmother: depression and who has received ECT with good

results

Current Medications
• Bupropion (Wellbutrin XL) 450 mg/day (thinks it is helpful as she

worsens if she tries to taper)
• Ziprasidone (Geodon, Zeldox) 60 mg in the morning and 180 mg at

night (unsure if this is helpful)
• Lamotrigine (Lamictal) 200 mg in the morning and 150 mg at night

(thinks it is helpful for her mood)

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49

PATIENT FILE

• Gabapentin (Neurontin) 300 mg in the morning, 600 mg at noon,
and 900 mg at night; occasional 100 mg as needed for breakthrough
anxiety (experiences intolerable return of anxiety at much lower doses)

• Pramipexole (Mirapex) 1 mg/night for restless legs syndrome (unclear
whether helpful)

• Methylphenidate extended-release (Concerta) 54 mg/day for daytime
sleepiness (thinks it is helpful)

• Sodium oxybate (Xyrem) 9 mg in one dose at night for narcolepsy and
daytime sleepiness (not taken in recommended split dose)

• DDAVP (the peptide Desmopressin) 0.4 mg/night for bedwetting

Based on just what you have been told so far about this patient’s history

and current symptoms, would you consider her to fall within the bipolar

spectrum?

• Yes
• No

Would you continue her “mood stabilizing” medications?

• Yes, continue both ziprasidone (Geodon) and lamotrigine (Lamictal)
• Continue ziprasidone but discontinue lamotrigine
• Continue lamotrigine (Lamictal) but discontinue ziprasidone (Geodon)
• No, discontinue both ziprasidone (Geodon) and lamotrigine (Lamictal)

Attending Physician’s Mental Notes: Initial Psychiatric
Evaluation
• Nothing unexpected on mental status examination which showed

depression and anxiety
• Because she has had numerous recurrences, this makes her illness

appear to be somewhat unstable; however, she has not shown any
overt signs of bipolarity

• The best diagnosis for this patient may be severe generalized anxiety
with major depressive recurrent unipolar disorder

• Nevertheless, tactics that are useful for bipolar mood disorders may
be useful in this patient

• Continuing ziprasidone (Geodon) and lamotrigine (Lamictal) may help
mitigate the risk of a future relapse

• Thus, these medications were continued at the time of the initial
evaluation

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50

PATIENT FILE

Further Investigation:
Is there anything else you would especially like to know about this

patient?

• What about details concerning the diagnosis of narcolepsy and of
restless legs syndrome, the treatments given and the responses to
those treatments?

– During the past year as her depression has recurred and worsened,
she has developed excessive daytime sleepiness

– She had an overnight sleep polysomnogram done in another city
that supposedly showed sleep onset REM (rapid eye movement)
periods, but you do not have a copy of the report and do not know
if it was done while taking any medications, or after the withdrawal
of any medications

– During the past year she has also complained of restless legs
worse in the evening when trying to fall asleep

– Because of her diagnosis of narcolepsy, she was prescribed
methyphenidate extended release (Concerta) which helps a bit for
her daytime sleepiness, but because she was still sleepy, sodium
oxybate (Xyrem) was added without further improvement of
daytime alertness although she gets to sleep right away and also
sleeps well through the night now

– In fact, she sleeps too well through the night now, and has
bed wetting, for which she has been prescribed DDAVP
(Desmopressin), but it is not very helpful

– Because of her diagnosis of restless legs syndrome, she is
prescribed pramipexole (Mirapex), with equivocal results

Based on what you know so far about this patient’s history, current.

symptoms, and treatment responses, are you convinced her daytime

sleepiness and nighttime restlessness are adequately diagnosed and

treated?

• Yes
• No

Would you continue her 4 sleep disorder medications?

• Yes, continue all 4 (methylphenidate (Concerta), sodium oxybate
(Xyrem), DDAVP (Desmopressin) and pramipexole (Mirapex))

• No, stop one or more of these

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51

PATIENT FILE

Attending Physician’s Mental Notes: Initial Psychiatric
Evaluation, Continued
• The patient’s complaint of excessive daytime sleepiness can be

diffi cult to assess given all the medications she is taking, especially
sodium oxybate (Xyrem) and gabapentin (Neurontin), which can cause
excessive daytime sleepiness

• It can also be diffi cult to determine whether her sleepiness represents
narcolepsy or really represents “hypersomnia” as an associated
symptom of depression

• It can be similarly diffi cult to determine whether her restless legs
represent restless legs syndrome or really represent psychomotor
agitation as an associated symptom of anxiety or whether restless
legs represent a side effect of bupropion (Wellbutrin) rather than
restless legs syndrome

• It is even possible that her sleep disorder treatments are interfering
with her treatments for depression and anxiety

• Thus, her sodium oxybate (Xyrem) was tapered, and then her DDAVP
(Desmopressin) discontinued, and her pramipexole (Mirapex) was
also tapered over the next month following her initial assessment

Case Outcome: First and Second Interim Followup Visits,
Weeks 2 and 4
• The patient experienced some initial insomnia and restless sleep

as sodium oxybate (Xyrem) was withdrawn, but this resolved in
several days, as did her incontinence; her daytime sleepiness actually
improved somewhat but she continued to have problems falling asleep
some nights

• Next, her pramipexole (Mirapex) was tapered without worsening of
restless legs, or of insomnia, or mood

• Finally, her daytime gabapentin (Neurontin) was tapered to half
dose with improvement in daytime sleepiness, but this was only
intermittently tolerated, because of re-emergence of anxiety; however,
higher gabapentin (Neurontin) doses caused daytime sleepiness

• She continued to have depression; also, her anxiety continued to
wax and wane day and night, with some relief by additional doses of
gabapentin (Neurontin), but, unsatisfactory overall results; if anxiety
and agitation occur at night, she also has insomnia

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52

PATIENT FILE

Considering her former response and side effects with ECT treatment,

would you consider using an alternative non-drug treatment method for

her refractory symptoms?

• Yes, consider ECT
• Yes, consider VNS
• Yes, consider TMS
• Yes, consider DBS

Attending Physician’s Mental Notes: Second Interim Followup,
Week 4
• The patient’s prior response to ECT suggests that it, or a similar

treatment, may be benefi cial
• She is hesitant to try ECT again because of the memory loss she

sustained, but may benefi t from another alternative treatment strategy
• Vagal nerve stimulation (VNS) (approved for treatment-resistant

depression and available at the time of this evaluation)
– VNS involves surgical implant of a stimulation device in the upper

left side of the chest (intended as a permanent implant, though it
can be removed)

– The pulse generator can be programmed to deliver electrical
impulses to the vagus nerve at various durations, frequencies, and
currents

– Stimulation typically lasts 30 seconds and occurs every fi ve
minutes

– After an initial wave of enthusiasm for this treatment, use of VNS
for depression has waned due to disappointing results, high

costs and some complications, include the hassle of having the
stimulator and electrode removed

• Transcranial magnetic stimulation (TMS) (approved for treatment-
resistant depression)
– Generally done on an outpatient basis
– Electromagnetic coil is placed against the scalp near the forehead

and turned off and on repeatedly for 30 to 50 minutes per treatment
– Typical treatment duration is fi ve daily treatments a week for four to

six weeks
– Insurance coverage is variable for a course of this treatment which

costs several thousand dollars
– TMS has been best studied in patients who have failed a single

antidepressant, and not for more complicated cases, or in cases
with prior good or bad responses to ECT, so it is diffi cult to predict
the chances of success for this patient

• Deep brain stimulation (DBS) (in trials for treatment-resistant
depression)

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53

PATIENT FILE

– Involves two surgical procedures, one to implant electrodes in the
brain and a second to implant a neurostimulator in the chest

– Stimulation is generally constant but can be temporarily turned off
by holding a magnetic device over the area of the chest where the
neurostimulator is located

– DBS is an experimental procedure available at only a few medical
centers with research protocols that may cover some or all of the
costs

– Risks and benefi ts of DBS remain unknown in treatment resistant
depression, so DBS is reserved for patients who have failed many
treatments, such as this patient

• After discussion of these options, the patient asked to defer action on
them so she could research VNS, TMS and DBS, and in the meantime,
she asked to try some other medications

Would you continue her methylphenidate extended release (Concerta)

for daytime sleepiness?

• Yes
• No

Attending Physician’s Mental Notes: Second Interim Followup,
Week 4, Continued
• On one hand, methylphenidate extended release (Concerta) seems

to be helpful for her daytime sleepiness and one could even consider
raising the dose to try to alleviate her depression

• On the other hand, this could risk making her anxiety worse and, to
the extent that daytime sleepiness is related to sedating medications’
side effects, it may be better to adjust those

• For now, the patient is not willing to stop the stimulant, and after a
discussion of risks and benefi ts, methylphenidate was continued

• Spoke with husband who is supportive and denies any marital confl ict

Would you consider adding any of the following medications to her

regimen?

• Lithium (to boost mood and mitigate risk of cycling)
• Monoamine oxidase inhibitor (MAOI) (to boost mood)
• Mirtazapine (Remeron) (to boost mood and possibly treat anxiety)
• Quetiapine (Seroquel) (to boost mood and possibly treat anxiety)
• Aripiprazole (Abilify) (to boost mood)
• None of these

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54

PATIENT FILE

Attending Physician’s Mental Notes: Second Interim Followup,
Week 4, Continued
• Lithium
– Could help to boost her mood and mitigate risk of future relapse
– If added it may not be necessary to give her a full dose as she is

already on other mood stabilizing medications
• MAOI
– May help boost mood, as this has been effective for patients with

anxious depression
– However, this could also be activating for some patients and cause

problems with sleep and anxiety
– If added, an MAOI would require discontinuation of bupropion
– Transdermal selegiline (Emsam) does not require dietary restriction

and may be a preferable formulation
• Mirtazapine (Remeron)
– May boost mood and also potentially treat anxiety
• Quetiapine (Seroquel)
– May boost mood (approved for depressed phase of bipolar disorder

and as adjunct for unipolar depression)
– May also be helpful for anxiety (anecdotal reports as adjunct)
– If added, it may require careful dosing to avoid daytime sedation
• Aripiprazole (Abilify)
– May boost mood (approved as adjunct for unipolar depression)
– Can be activating and cause problems with anxiety
• The patient was encouraged to switch from bupropion (Wellbutrin)

to mirtazapine (Remeron), but instead opted for aripiprazole (Abilify)
augmentation of her current medications (bupropion, lamotrigine,
gabapentin, methylphenidate), while discontinuing ziprasidone.

Case Outcome: Multiple Interim Followups to Week 24
• Aripiprazole (Abilify) titration from 2 mg to 5 mg while ziprasidone

(Geodon) was discontinued showed no real changes good or bad for
the fi rst month (week 12)

• Aripiprazole was then increased to 10 mg, with slight improvement
(week 16)

• After a second month at 10 mg of aripiprazole, no further
improvement in depression and anxiety and overall results not
satisfactory (week 20)

• The patient was switched from aripiprazole to quetiapine (Seroquel),
which was not associated with improvement of mood or anxiety, and
made her sleepiness worse (by week 24)

• The patient was offered a trial of mirtazapine (Remeron) again, and

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55

PATIENT FILE

due to the results with quetiapine, was not willing to take it (at week
24)

• She was offered an MAOI, but said she would rather consider VNS,
TMS or another round of ECT (at week 24)

• Insurance approved VNS, and the patient became essentially
asymptomatic for more than 4 years

Case Debrief
• The patient has a 25-year history of recurrent anxiety and depression

that appears unipolar in nature and has been somewhat responsive to
antidepressants and very responsive to ECT in the past

• Her current relapse is causing her disability and is not fully responsive
to the 8 medications she was taking on initial referral (bupropion,
lamotrigine, ziprasidone, gabapentin, sodium oxybate, DDAVP,
methylphenidate and pramipexole)

• It seems possible that her sleep symptoms are more related to her
anxious depression rather than to additional diagnoses of narcolepsy
and restless legs syndrome and, in any event, her treatments for these
sleep disorders did not improve her symptoms; discontinuation of
several sleep medications (sodium oxybate, pramipaxole and DDAVP)
if anything improved her symptoms; other clinicians may have opted
to continue these medications

• Following simplifi cation of her medication regimen from 8 medications
to 5, she failed to respond to augmentation with aripiprazole or with
quetiapine

• Possibly because of her prior response to ECT (and a fi rst degree
relative also responded to ECT), she was an excellent candidate for
VNS

Take-Home Points
• It can be diffi cult to determine whether insomnia with anxiety

and psychomotor agitation at night, with simultaneous excessive
sleepiness during the day while having poor sleep at night in a patient
taking sedating medications, are due to a sleep disorder, to an anxiety
disorder, to a depressive disorder or to side effects of medications

• Simplifying medication regimen from 8 medications to 5 may help
determine whether some of the symptoms are due to medications and
whether all medications are necessary

• The ultimate proof that her symptoms of daytime sleepiness and night
time agitation are linked to her anxiety/mood disorder rather than to
sleep disorders was that these symptoms abated when her depression
and anxiety abated with effective treatment by VNS

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56

PATIENT FILE

Performance in Practice: Confessions of a
Psychopharmacologist
• What could have been done better here?
– Did it take too long to get to the VNS recommendation?
– Should she have been pushed harder to try mirtazapine or an

MAOI rather than augmentation with two additional, three total,
atypical antipsychotics?

– Did it take too long to clarify the sleep issues?
– Should we have tried harder to get a copy of the written results of

the polysomnogram?
• Possible actions for improvement in practice
– Make sure that augmentation with atypical antipsychotics is not

the only option offered, or the only option offered early, since these
drugs are expensive and can have notable side effects

– Despite less robust comparative data, agents such as mirtazapine
and MAOIs, and also VNS and ECT, can be considered earlier in the
treatment algorithm

– Get husband more involved as patient is at high risk for long term
depression, and he is her major support system

– Consider psychotherapy earlier rather than after VNS and assess
whether the patient is a good candidate for interpersonal or
cognitive behavioral approaches

Tips and Pearls
• Treatment with pregabalin (Lyrica), approved for anxiety in Europe

but not in the US, rather than gabapentin (Neurontin), not approved
anywhere for anxiety, may be less sedating if more expensive

• If the patient requires an MAO inhibitor, best to stop the bupropion
and the methylphenidate, but lamotrigrine and gabapentin can be
continued. For heroic cases unresponsive to an MAO inhibitor,
stimulants such as methylphenidate can sometimes be cautiously
added to an MAO inhibitor by experts monitoring cardiovascular status
who are sophisticated about weighing risks and benefi ts

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57

PATIENT FILE

Two-Minute Tute: A brief lesson and psychopharmacology
tutorial (tute) with relevant background material for this case
– Classifi cation and testing for narcolepsy, hypersomnia and

restless legs syndrome
– Overlap of symptoms in sleep disorders with psychiatric

disorders

International Classifi cation Of Sleep Disorders
Diagnostic Criteria Of Narcolepsy
• Patient complains of excessive sleepiness or sudden muscle

weakness

• Recurrent daytime naps or lapses into sleep almost daily for at
least 3 months

• Possible sleep-onset REM (rapid eye movement) periods,
hypnagogic hallucinations, and sleep paralysis

• With cataplexy

• Sudden bilateral loss of postural muscle tone in association
with intense emotion

• Hypersomnia not better explained by another disorder

• Should be confi rmed by PSG (polysomnogram) followed by
MSLT (multiple sleep latency test, see below) which should show
a mean sleep latency of 8 minutes and two more sleep-onset
REM periods (SOREMPs) following normal sleep

• May be confi rmed by orexin levels in the cerebrospinal fl uid
(CSF) <110 pg/ml or, 1/3 of mean normal control levels

Narcolepsy is estimated to occur in 0.03–0.16% of the general population,
with its development mostly beginning in the teens. Narcoleptic sleep
attacks usually occur for 10–20 minutes and, on awakening, the patient
can be refreshed for 2–3 hours before feeling the need to sleep again.
Although sleep attacks occur most often in a monotonous situation, they
can also occur when a person is actively conversing or eating. Symptoms
of narcolepsy may include frightening hypnogogic hallucinations and
sleep paralysis, which are usually coincident with SOREMPs. Not
everyone with narcolepsy will have cataplexy but it is a unique feature of
this disorder. An attack normally lasts a few seconds to minutes, during
which the person is conscious. Some people have only minimal muscle
involvement, while others can have “full-body” attacks; however, the
respiratory and ocular muscles are never involved. Excessive sleepiness
is the main symptom to continue with age, and it may worsen alongside
the development of periodic limb movements and obstructive sleep apnea.
In addition, sleep may be disrupted and include frequent awakenings
(International Classifi cation of Sleep Disorders, revised, 2001).

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58

PATIENT FILE

Multiple Sleep Latency Test (MSLT)

• Dark comfortable room at an ambient temperature

• Smoking, stimulants and vigorous physical activity avoided
during the day, only light breakfast and lunch given

• Instructions are to

– “Lie quietly in comfy position, keep eyes closed, try to fall
asleep”

• Five nap opportunities as 2 hour intervals – initial nap
opportunity 1.5–3 hours after termination of usual sleep

• Between naps patient out of bed and awake

• Sleep onset determined by time from “lights out” to fi rst epoch of
any sleep stage

• To assess occurrence of REM sleep the test continues for 15
minutes from fi rst sleep epoch

• Session terminated if sleep does not occur after 20 minutes

The Multiple Sleep Latency Test is carried out in sleep laboratories often
after a night of PSG and a week fi lling in a sleep diary.

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59

PATIENT FILE

The Epworth Sleepiness Scale (ESS) is a self-rating tool to enable patients
and physicians to easily investigate problems with excessive sleepiness.
For the most part it can be used both for looking at a day as a whole or
for various times throughout a person’s wake time to chart their circadian
changes. As a self-rating tool, it is of course subjective and may not
correlate well with objective test measures.

For the general population the average score on the ESS may be
approximately 9 where as scores over 11 indicate excessive sleepiness.
Interestingly those with insomnia may have scores lower than the general
population, lending further weight to the theory that insomnia is a disorder
of the arousal mechanisms that, as well as keeping someone awake at
night, can leave someone in a state of hyperarousal during the day.

Likelihood of falling asleep or dozing off when:

Sitting and reading 0 1 2 3

Watching television 0 1 2 3

Sitting inactive in a public place – theater, meeting 0 1 2 3

As a car passenger for an hour without a break 0 1 2 3

Lying down to rest in the afternoon 0 1 2 3

Sitting and talking to someone 0 1 2 3

Sitting quietly after lunch without alcohol 0 1 2 3

Stopped for a few minutes while driving a car 0 1 2 3

Total Score

Chance of Dozing:

The Epworth Sleepiness Scale (ESS)

Likelihood scale – rate each from 0–3 and total score

0 – would never doze 2 – moderate chance of dozing
1 – slight chance of dozing 3 – high chance of dozing

Score over 11 indicates abnormal sleepiness

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60

PATIENT FILE

Cardinal diagnostic features of RLS (restless legs
syndrome)

1 Urge to move limbs usually associated with paresthesias or
dysesthesias

2 Symptoms start or become worse with rest

3 At least partial relief with physical activity

4 Worsening of symptoms in the evening or at night

Patients with RLS experience an urge to move their legs to rid themselves
of unpleasant sensations (prickling, tingling, burning or tickling;
numbness; “pins and needles’’ or cramp-like sensations). This movement
typically relieves the sensations, which can occur at any time but are
most disruptive when one is trying to fall asleep.

Primary hypersomnia

Differential Diagnosis

• Substance-induced hypersomnia
Drug of abuse
Medication use
Exposure to a toxin

• Psychiatric disorder
Major depressive disorder
Depressed phase of bipolar disorder

• Sleep deprivation
Symptoms reversed with increased sleep

• Post-traumatic hypersomnia
Head trauma
CNS injury

• Delay- or advance-phase sleep syndrome
Circadian rhythm is shifted

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PATIENT FILE

Differential diagnosis in patients with hypersomnia disorders can be
diffi cult, but is important in choosing the best treatment. The diagnosis
of primary hypersomnia is reserved for those patients in whom no other
factor can be considered causal to the symptom of sleepiness.

Diagnostic measures in narcolepsy and hypersomnia

(data from Bassetti et al 2003)

ESS = Epworth Sleepiness Scale
MSLT = Multiple Sleep Latency Test
Lat = latency
SOREMP = Sleep onset REM Periods
CSF = Cerebrospinal Fluid

ESS MSLT
Lat.

(min)

MSLT #
SOREMP

CSF
Hypocretin

pg/ml

Narcolepsy with
Cataplexy

18 3.38 3.5 96.5

Narcolepsy without
Cataplexy

19 2.75 2.5 277.3

Primary Hypersomnia 17 6 0 226.8

Hypersomnia in
Psychiatric Disorders

18 7.83 0 278

Major
Depressive

Disorder

Attention
Defi cit
Hyperactivity
Disorder

Narcolepsy Obstructive
Sleep Apnea

Shift-Work
Sleep
Disorder

Mood +++ – – + –

Sleepiness + + +++ +++ +++

Fatigue ++ + ++ ++ ++

Concentration ++ +++ ++ ++ ++

Overlap of symptoms in sleep and psychiatric disorders

Many of the symptoms seen in sleep disorders are common in psychiatric
disorders and vice versa. This chart compares the frequency of different
symptoms among common sleep and psychiatric disorders, which is
useful in making a differential diagnosis. The degree of symptom overlap
among many disorders emphasizes the need to be able to recognize and
treat a patient’s individual symptoms, rather than use a single treatment
strategy for all symptoms of a disorder.

Disorder

Symptom

+++ Most Common ++ Common + Average – None

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PATIENT FILE

Posttest Self Assessment Question: Answer
Which of the following are approved treatments for treatment resistant

depression?

A. Deep brain stimulation (in trials for treatment-resistant depression but
not approved)

– Involves two surgical procedures, one to implant electrodes in the
brain and a second to implant a neurostimulator in the chest

– Stimulation is generally constant but can be temporarily turned off
by holding a magnetic device over the area of the chest where the
neurostimulator is located

– This is an experimental procedure available at only a few medical
centers with research protocols that may cover some or all of the
costs

– Risks and benefi ts remain unknown so this is reserved for patients
who have failed many treatments

B. Transcranial magnetic stimulation (approved for treatment-resistant
depression)

– Generally done on an outpatient basis
– Electromagnetic coil is placed against the scalp near the forehead

and turned off and on repeatedly for 30 to 50 minutes per
treatment

– Typical treatment duration is fi ve daily treatments a week for four to
six weeks

– Insurance coverage is variable for a course of this treatment which
costs several thousand dollars

– TMS has been best studied in patients who have failed a single
antidepressant, and not necessarily indicated for more complicated
cases, or for cases with multiple antidepressant failures or failure
of ECT

C. Vagal nerve stimulation (approved for treatment-resistant depression)
– Involves surgical implant of a stimulation device in the upper left

side of the chest (intended as a permanent implant, though it can
be removed)

– The pulse generator can be programmed to deliver electrical
impulses to the vagus nerve at various durations, frequencies, and
currents

– Stimulation typically lasts 30 seconds and occurs every fi ve
minutes

– Studied in patients with more treatment failures than those patients
studied with TMS, aripiprazole, or quetiapine

– After an initial wave of enthusiasm for this treatment, use of VNS
for depression has waned due to disappointing results, high

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63

PATIENT FILE
costs and some complications, include the hassle of having the
stimulator and electrode removed

D. Aripiprazole (Abilify)(approved for treatment resistant depression)
– Studied in patients with major depression who did not have an

adequate response to one SSRI (Serotonin Selective Reuptake
inhibitor) or one SNRI (Serotonin Norepinephrine Reuptake
Inhibitor) antidepressant

– Not known how well it works in patients with failures to more
antidepressant treatments

E. Quetiapine (Seroquel)(approved for treatment resistant depression)
– Also studied in patients with major depression who did not have an

adequate response to one antidepressant
– Also not known how well it works in patients with failures to more

antidepressants
F. MAO inhibitors (not approved for treatment resistant depression)
– Although almost always used for treatment resistant depression

and almost never used fi rst line, is currently only approved for fi rst
line use and not for treatment resistant depression

• Clinical practice and numerous anecdotes suggest that some
patients who do not respond to one or more antidepressants,
including ECT, may respond to MAO inhibitors, but no controlled
studies. Activating for some patients and may cause problems with
sleep and anxiety

Answer: B, C, D and E

References
1. Stahl SM, Antidepressants, in Stahl’s Essential

Psychopharmacology, 3rd edition, Cambridge University Press, New
York, 2008, pp 511–666

2. Stahl SM, Disorders of Sleep and Wakefulness and their Treatment,
in Stahl’s Essential Psychopharmacology, Cambridge University
Press, New York, 2008, pp 815–862

3. Stahl SM, Aripiprazole, in Stahl’s Essential Psychopharmacology The
Prescriber’s Guide, 3rd edition, Cambridge University Press, New
York, 2009, pp 45–50

4. Stahl SM, Quetiapine, in Stahl’s Essential Psychopharmacology The
Prescriber’s Guide, 3rd edition, Cambridge University Press, New
York, 2009, pp 459–

64

5. Stahl SM, Gabapentin, in Stahl’s Essential Psychopharmacology The
Prescriber’s Guide, 3rd edition, Cambridge University Press, New
York, 2009, pp 221–225

6. Silberstein S, Marmura M, Stahl SM (Ed), Pramipexole, in

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64

PATIENT FILE
Neuropharmacology: The Prescriber’s Guide, Cambridge University
Press 2010, pp 262–265

7. Stahl SM, Diagnosis and Treatment of Sleep Wake Disorders, NEI
Press, Carlsbad, California, 2007

8. Stahl SM, Sleep: Excessive Sleepiness, NEI Press, Carlsbad,
California, 2005

9. Marangell LB, Martinez M, Jurdi RA et al. Neurostimulation
Therapies. Acta Psychiatrica Scandinavica 2007; 116: 174–181

10. Bassetti C, Gugger M, Bischof M et al. The narcoleptic borderland: a
multimodal diagnostic approach including cerebrospinal fl uid levels
of hypocretin-1 (orexinA). Sleep Medicine 2003; 4: 7–12

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