NURS 6630 Week 7 discussions Week 7 discussion Case #2 – The figment of a man who looked upon the lady
NURS 6630 Week 7 discussions Week 7 discussion Case #2 – The figment of a man who looked upon the lady sample nursing paper
PATIENT FILE
The Case: The figment of a man who looked upon the lady
The Question: Are atypical antipsychotics anti-manic, antidepressant,
anxiolytic, and hypnotic as well?
The Psychopharmacological Dilemma: How to improve insomnia that is
caused by depression, anxiety, mood swings, and hallucinations
Pretest self-assessment question (answer at the end of the case)
Which of the following properties of certain atypical antipsychotics lend to
their ability to promote and maintain sleep?
A. Histamine-1 receptor antagonism
B. Serotonin-2A receptor antagonism
C. Serotonin-7 receptor antagonism
D. A and B
E. All of the above
Patient evaluation on intake
• 42-year-old woman with a chief complaint of depression and
interpersonal stress
Psychiatric history
• The patient states she was horribly abused as a child and had been
addicted to alcohol and other substances for many years. Now has been
sober for 10 years and attends AA and Narcotics Anonymous (NA)
routinely with good results
• Admits moderate levels of PTSD symptoms with nightmares,
flashbacks, and panic attacks
• Routinely experiences dysthymia (persistent depressive disorder) with
intermittent full MDEs
Need paper help on Psychopharmacological assignments?
NURS 6630 Week 7 discussions Week 7 discussion Case #2 – The figment of a man who looked upon the lady
• Psychiatric review of symptoms suggests symptoms of
marked mood lability, affective dyscontrol, empty depression,
dissociative events consistent with mild borderline personality
disorder (BPDO)
• There is no history of inpatient psychiatric admissions, and rarely any
suicidal gestures or self-injurious behaviors
• Denies hallucinations and delusions, but states she is paranoid that
people might mean her harm and always needs to “be aware of her
environment”
• She has been in legal trouble for reacting to social situations by
striking out
– This occurs usually when narcissistic injury occurs or if emotions
are triggered by reminders of past abuse
147
Nurs 6630 case #2 The figment of a man who looked upon the lady, Walden University
Downloaded from http://stahlonline.cambridge.org
by IP 192.168.60.239 on Tue Jan 02 23:33:28 GMT 2018
Stahl Online © 2018 Cambridge University Press.
All rights reserved. Not for commercial use or unauthorized distribution.
PATIENT FILE
• The patient has been tried on
– One SSRI, paroxetine (Paxil) 40 mg/d
– One TCA, nortriptyline (Pamelor) 75 mg/d
• Both monotherapies allowed for moderate improvements in her
symptoms at best
• Has attended supportive psychotherapy weekly for many years
• Attends AA or NA daily and has a sponsor who is supportive
Social and personal history
• Single, never married, and has no children
• Has a General Education Diploma and attends college classes
sporadically now
• Past alcohol and SUD, but has been in remission for 10 years
• No current legal issues but has some financial hardships
Medical History
• Patient is overweight
• Has CAD, DM2, chronic obstructive pulmonary disease (COPD),
hyperlipidemia, GERD, HTN, glaucoma
• Compliant with her primary care clinician who collaborates well with her
psychiatrist
Family History
• MDD in mother and aunts
• SUD throughout her extended family
• GAD in her mother
• Possible ADHD in siblings
Current psychiatric medications
• Paroxetine (Paxil) 40 mg/d (SSRI)
Current medical medications
• Exenatide (Byetta)
• Metformin (Glucophage)
• Glipizide (Glucotrol)
• Ramipril (Altace)
• Albuterol (Ventolin inhaler)
• Fluticasone/salmeterol (Advair Diskus)
• Latanoprost (Xalatan)
• Ezetimibe (Zetia)
• Pravastatin (Pravachol)
• Protonix (Pantoprazole)
148
Downloaded from http://stahlonline.cambridge.org
by IP 192.168.60.239 on Tue Jan 02 23:33:28 GMT 2018
Stahl Online © 2018 Cambridge University Press.
All rights reserved. Not for commercial use or unauthorized distribution.
PATIENT FILE
Question
Based on this patient’s history and the available evidence, what might you do
next, given that she still has moderate, residual depression and PTSD
symptoms?
• Try another SSRI
• Switch to an SNRI
• Augment with a mood stabilizer
• Augment with an NDRI, like bupropion-XL (Wellbutrin-XL)
• Augment with a 5-HT1A receptor partial agonist, like buspirone (BuSpar)
• Augment with an atypical antipsychotic
Attending physician’s mental notes: initial evaluation
• Patient has worked hard on sobriety and even to control her personality
disorder symptoms
• She is clearly depressed and agitated with PTSD
• At the time, the only other approved agent for PTSD was sertraline (Zoloft),
an SSR
• Buspirone (BuSpar) and bupropion-XL (Wellbutrin-XL) are widely used,
off-label depression augmentation options, which might help her
• Perhaps it is best to see what symptoms the patient deems most
important to treat first, PTSD or depression
• As she is overweight with metabolic comorbidities, it may be worth
choosing medications that limit risk of weight gain
Further investigation
Is there anything else you would especially like to know about this patient?
• What symptoms does the patient consider critical?
– Insomnia – she does not sleep well in general and this may be
caused either by depression, PTSD, or her current SSRI
– Nightmares and flashbacks – these are very problematic as they
trigger in the patient other symptoms such as mood lability and
potential for violence and drug use
– Depression – for her, this is secondary. Her depression is usually caused
by PTSD flare-ups, their aftermath, and her interpersonal stressors
– She feels that controlling her PTSD and sobriety will mitigate her
depression
Question
Based on what you know about this patient’s history, current symptoms,
and medication, what would you do now?
• Try another SSRI
• Switch to an SNRI
149
Downloaded from http://stahlonline.cambridge.org
by IP 192.168.60.239 on Tue Jan 02 23:33:28 GMT 2018
Stahl Online © 2018 Cambridge University Press.
All rights reserved. Not for commercial use or unauthorized distribution.
PATIENT FILE
• Augment with a mood stabilizer
• Augment with bupropion-XL (Wellbutrin-XL)
• Augment with buspirone (BuSpar)
• Augment with a sedating atypical antipsychotic
• Augment with prazosin (Minipress)
• Augment with a BZ sedative–hypnotic
• Augment with a melatonin receptor agonist hypnotic
• Augment with an antihistamine hypnotic
Attending physician’s mental notes: initial evaluation
(continued)
• Given the higher burden of PTSD and that she is failing an SSRI that is
approved for PTSD and MDD, she will need to be tapered off and
switched to another medication
• Will need to make a decision to try to treat all of her symptoms at once or
treat single target symptoms in order of severity
• Formal CBT, such as exposure therapy for PTSD, is not available in the
community and she has good rapport with her supportive therapist and
her sponsors; therefore, these treatments should continue
• The other approved medication for PTSD is sertraline (Zoloft), which
makes clinical, regulatory, and guideline-based sense
• Avoiding potentially addictive products is clearly warranted
Case outcome: interim follow-ups through three months
• Next, she is cross-titrated off paroxetine (Paxil) and onto paroxetine-CR
(Paxil-CR)
• The patient states she has been on paroxetine (Paxil) for some time now
and is comfortable with it as it has helped partially
• As informed consent is given, steering her away from continued
paroxetine use, her resistance increases
• States paroxetine at higher doses in past has been problematic for her
– She is offered a newer option and she states she would like to try the
slow-release CR preparation
– It is titrated to 50 mg/d
– There is no clear benefit
• Is offered a switch to another SSRI, sertraline (Zoloft), or to use a
combination strategy bupropion-XL (Wellbutrin-XL)
• After weighing the options and giving informed consent, knowing that
sertraline (Zoloft) is mechanistically similar to her paroxetine-XR
(Paxil-CR), she opts for the NDRI bupropion-XL (Wellbutrin-XL)
combination in the hope of a different outcome than with her SSRI, but
also that it may curb her weight and improve her energy
150
Nursing class assignments giving you trouble? Let our writers help you. Order now a top-notch nursing paper.
Downloaded from http://stahlonline.cambridge.org
by IP 192.168.60.239 on Tue Jan 02 23:33:28 GMT 2018
Stahl Online © 2018 Cambridge University Press.
All rights reserved. Not for commercial use or unauthorized distribution.
PATIENT FILE
• Titrated up to 450 mg/d as a combination with the SSRI, and the
depression and vegetative symptoms do improve somewhat, but she
continues with her usual partially treated PTSD symptoms and insomnia
Considering her current medication regimen, do you have any concerns?
• Does she have a history of seizures or eating disorder, as bupropion
products may induce seizures in these patients?
– She does not
• The paroxetine-CR (Paxil-CR) is a robust inhibitor of the p450 2D6
enzyme system, for which bupropion products are a substrate
– Is it possible that this drug interaction might elevate her bupropion
plasma levels and induce a seizure?
Nurs 6630 case #2 The figment of a man who looked upon the lady, Walden University
• She is benefitting from this combination
– Perhaps bupropion levels might be drawn, or
– Perhaps augmenting her remaining PTSD symptoms with an
antiepileptic medication might be a win–win situation, where
symptoms and side effects are reduced simultaneously
Attending physician’s mental notes: six months
• At the time of this treatment, the CYP450 interaction was a notable
concern but this patient was significantly overweight, which likely
accommodated this higher end of normal approved dosing
• Her depression appears well treated now but her PTSD residual
symptoms continue to be problematic
• As she had modest gains from her first two medications, an SSRI and an
NDRI, stopping them might cause relapse
• Adding another augmentation is likely warranted now, using a specific
target symptom approach
Case outcome: interim follow-ups through nine months
• The patient agrees to augmentation with the antiepileptic selective GABA
reuptake inhibitor (SGRI) tiagabine (Gabitril)
• This agent is not addictive, and in theory should elevate GABA
availability, promote anxiolysis, and also protect against
bupropion-induced seizures
• This augmentation was supported at this time by open-label trials but
had no sanctioned approvals
– Titrated to 16 mg/d
– Sleep improves, but no other clear effects on the PTSD reliving events
– It should be noted that this drug failed in controlled monotherapy
trials in the treatment of PTSD some years later, and was also given a
warning that despite being an approved epilepsy treating medication,
it could actually cause seizures in non-epileptics
– This patient suffered no such complications, however
151
Downloaded from http://stahlonline.cambridge.org
by IP 192.168.60.239 on Tue Jan 02 23:33:28 GMT 2018
Stahl Online © 2018 Cambridge University Press.
All rights reserved. Not for commercial use or unauthorized distribution.
PATIENT FILE
Case outcome: interim follow-ups through 12 months
• The patient gradually presents with more difficulty as random social
events trigger PTSD reliving and some mood lability occurs
– There are increased psychosocial stressors and a return of
depressive symptoms
– Sobriety continues
– PTSD symptoms increase
– Outside her usual insomnia and nightmares, she now has “a little
man watching her”
◦ Upon investigation, it is determined that she has a visual
hallucination of a small man staring down at her when she is on
the verge of falling asleep (hypnagogic hallucination)
◦ This hallucination is not related to any PTSD themes, but she
finds it very disturbing
Clinically, what types of patients typically suffer hypnagogic
hallucinations?
• Narcolepsy patients
• Narcoleptics also may suffer sleep paralysis, cataplexy (drop attacks),
as well as their usual REM-onset sleep attacks
• In this case, these hallucinations could also be related to a relapse into
drug use or seizure activity (both of which were negative)
Case outcome: interim follow-ups through 12 months (continued)
• Evaluated for sleep disorder
– Found to have OSA
– Prescribed a continuous positive airway pressure (CPAP) machine
and is compliant with its use
• The OSA appears to be unrelated to the hallucinations
• There is no relapse into drug use to explain the hallucinations
• She is not having seizures
Question
What would you do now?
• Escalate the tiagabine (Gabitril)
• Augment with a 5-HT1A receptor partial agonist
• Augment with an anxiolytic or hypnotic agent that is not addictive
• Add an atypical antipsychotic
• Taper off the now ineffective medications and start a new regimen
Attending physician’s mental notes: 12 month follow-ups
• Despite increasing progress on her initial three medication regimen
(SSRI, NDRI, SGRI), this was thwarted by social stress and exposure
to PTSD-triggering stimuli
152
Downloaded from http://stahlonline.cambridge.org
by IP 192.168.60.239 on Tue Jan 02 23:33:28 GMT 2018
Stahl Online © 2018 Cambridge University Press.
All rights reserved. Not for commercial use or unauthorized distribution.
PATIENT FILE
• Given her increased mood lability, irritability, potential for violence,
flashbacks, and now limited hallucinations, an antipsychotic might be
warranted
• At this time, it was becoming known that the atypical antipsychotics
could drive an increase in weight but it was unclear if they would
increase the metabolic syndrome
• This patient already has the metabolic syndrome, but it is very well
controlled and followed very closely by her PCP
Case outcome: interim follow-up, 24 months
• This patient had fully relapsed
• The SSRI, paroxetine-CR (Paxil-CR), is discontinued due to its
ineffectiveness
• The SGRI tiagabine (Gabitril) is tapered off as it was only partially
effective, but mounting evidence suggests it may create seizures in
non-epileptic patients
• Continues on bupropion (Wellbutrin-XL) as she recollects this being the
most beneficial for her depressive symptoms. It also has halted her
weight gain and curbed her appetite
• Next, she starts the more SERT-selective SSRI escitalopram (Lexapro)
up to 20 mg/d to treat PTSD and residual depressive symptoms
• She is also given low-dose atypical antipsychotic quetiapine (Seroquel)
25–50 mg at bedtime to help induce sleep, possibly improve depression,
PTSD, and mood lability
– It is felt to be too risky to use a potentially addictive BZ
sedative–hypnotic, given her SUD history and well-maintained
sobriety
– This low-dose quetiapine is not expected to cause metabolic
complications
– If she has persistent hallucinations, then the dose could be increased
to full antipsychotic potential at doses greater than 400 mg/d
– Warned of low but possible TD/EPS risks
– Warned of metabolic risks and primary care clinician is consulted
• Does well on this combination and gradually has very good control of
depression and PTSD symptoms
• The “little man” leaves
• A few weeks later, the “little man” hallucination comes back but without a
full PTSD exacerbation
– The quetiapine (Seroquel) is increased to 100 mg at bedtime with
good effect once again
• A few weeks later, the patient has increased problems with lability and
anger at her AA and NA meetings, which is putting her sobriety at risk
153
Downloaded from http://stahlonline.cambridge.org
by IP 192.168.60.239 on Tue Jan 02 23:33:28 GMT 2018
Stahl Online © 2018 Cambridge University Press.
All rights reserved. Not for commercial use or unauthorized distribution.
PATIENT FILE
– Now offered a daytime 25–50 mg quetiapine (Seroquel) dose, which
is utilized with good effect
◦ In total, takes 150 mg daily along with the SSRI and NDRI
combination therapy
• After several weeks of no hallucinations and good affect control, she
opts to lower the atypical antipsychotic slowly to avoid prolonged
exposure and side effects
Are you having trouble completing your nursing paper assignments? Allow our writers to lighten your academic load. Order a high-quality nursing paper right now.
Nurs 6630 case #2 The figment of a man who looked upon the lady, Walden University
• This goes well clinically and she continues on her baseline SSRI plus
NDRI
Attending physician’s mental notes: 36-month follow-ups
• Patient now is fairly stable and doing better
• The SSRI and NDRI work well together
– Symptoms are much less problematic
– They appear to cancel each other’s side effects out in a win–win
scenario
– Denies side effects altogether
• There is no increase in metabolic issues with the short-term, low-dose
quetiapine (Seroquel) use, and an eye examination for cataracts was
negative
• Patient is compliant and we can extend her visits to quarterly, short
appointments while we continue her supportive psychotherapy
Case outcome and multiple interim follow-ups to 60 months
• The patient, throughout this time, has sustained months of doing very
well with regard to relationships, returning to school, and being active in
the community
• She has occasional mild flare-ups of PTSD and BPDO symptoms but
these are less frequent and less severe, likely as a result of ongoing
sobriety, supportive psychotherapy, and a consistent set of
well-tolerated medications
• Occasionally, increased PTSD nightmares and the “little man” return
– The patient self-titrates as-needed quetiapine (Seroquel) 50–150 mg
daily doses
◦ This treats insomnia and restores her sleep cycle
◦ This treats bedtime hallucinations
◦ This improves affective lability during the daytime
• It is also determined that she has two types of insomnia
– The spells mentioned here are usually PTSD related and fairly
extreme in the patient’s point of view
◦ The rapid onset of sleep, maintenance of sleep, and possible
antipsychotic effect of her atypical antipsychotic is warranted
and works well here
154
Downloaded from http://stahlonline.cambridge.org
by IP 192.168.60.239 on Tue Jan 02 23:33:28 GMT 2018
Stahl Online © 2018 Cambridge University Press.
All rights reserved. Not for commercial use or unauthorized distribution.
PATIENT FILE
– There is a second type of insomnia that is more insidious, where she
has difficulty initiating sleep, increasing her fatigue and irritability
with consequences next day
– Does not wish to take the atypical antipsychotic routinely as it was
“quite strong” with morning fatigue and potentially more serious
risks (TD/EPS/metabolic)
– For these transient bouts of insomnia that would last a few weeks at
a time, she was offered the MT1/MT2 receptor agonist approved,
non-addictive hypnotic (ramelteon [Rozerem] 8 mg at bedtime) with
good results and no side effects
• Now reliably alternates the quetiapine (Seroquel), ramelteon (Rozerem),
or no treatment, depending upon the type of sleep she is, or is not,
having
Case debrief
• The patient has the common comorbidity of MDD, PTSD, and SUD
• She has personality traits that leave her vulnerable to relapses
• She had an uncommon hypnogogic hallucination presentation
• She has been fairly stable now for many years likely due to sobriety,
sustained supportive psychotherapy, steady consistent medication
management with fully dosed and rationally used polypharmacy (instead
of many rapid medicine changes in reaction to new psychosocial,
adjustment disorders)
• The treating team was very good about communicating about the
patient’s situations, symptoms, and likely etiology (adjustment based
versus syndromal based) so that systems-based care was evident and
very effective
• The medication regimen continues in this fashion with continual good
results
Take-home points
• The patient had a balanced biopsychosocial approach by treating team
members and great support through the AA and NA communities and
her primary care team
– This is a win–win, textbook collaboration situation that ideally should
be emulated in these complex patient types, in that all providers were
communicating and working together
• The patient had, in addition, win–win polypharmacy situations
– Her SSRI and NDRI canceled out each other’s side effects while
providing additive clinical effectiveness regarding her many
comorbidities
– Her quetiapine (Seroquel) low dose was able to function as a
multipurpose drug in that it: (a) induced and (b) maintained
155
Downloaded from http://stahlonline.cambridge.org
by IP 192.168.60.239 on Tue Jan 02 23:33:28 GMT 2018
Stahl Online © 2018 Cambridge University Press.
All rights reserved. Not for commercial use or unauthorized distribution.
PATIENT FILE
her sleep, (c) alleviated her hallucination, and (d) provided
agitation control and mood stability during the day AND it did
not increase her metabolic disorder given its low dose and
intermittent use
• The atypical antipsychotics likely should not be considered firstline
drugs for insomnia, as they do carry risk for TD, EPS, and
metabolic disorder that approved and other off-label hypnotics do
not carry
Performance in practice: confessions of a
psychopharmacologist
• What could have been done better here?
– Hindsight is 20/20
– It likely was a bit risky, in terms of potential drug interactions,
having the patient on a full dose of paroxetine and bupropion
simultaneously
◦ If she happened to be a poor CYP450 2D6 enzyme metabolizer,
then her seizure risk could increase as her bupropion levels could
have elevated
◦ Use of tiagabine (Gabitril) in addition to these two medications
and the 2D6 interaction risk promoted an even greater seizure
risk
– Use of a more metabolically friendly atypical antipsychotic with a mild
to moderate sedating profile might have been preferred to the
quetiapine (Seroquel) used in this case (perhaps asenapine (Saphris))
• Possible action items for improvement in practice
– Memorize drug interaction tables or use software or the internet to
screen for interactions
– If more risky combinations are used, consider a blood draw
laboratory test for CYP450 isoenzyme quantification or drug levels
– Be aware that atypical antipsychotics possess positive mechanisms
for inducing and maintaining sleep that are not just side effects but
reasonable positive clinical effects
Nurs 6630 case #2 The figment of a man who looked upon the lady, Walden University
Tips and pearls
• Two SSRI antidepressants are approved for treating PTSD: paroxetine
(Paxil) and sertraline (Zoloft)
• In recent years, prazosin (Minipress) has acquired an evidence base to
support its off-label use in alleviating PTSD nightmares specifically. This
would have been a reasonable option in this case
• The beta-blockers have some limited evidence that, if utilized quickly
after a trauma, they blunt hyperautonomic responses and that the risk for
156
Downloaded from http://stahlonline.cambridge.org
by IP 192.168.60.239 on Tue Jan 02 23:33:28 GMT 2018
Stahl Online © 2018 Cambridge University Press.
All rights reserved. Not for commercial use or unauthorized distribution.
PATIENT FILE
developing full syndromal PTSD may be less. This would have been less
helpful in this case as her trauma was not recent
• The atypical antipsychotics and antiepileptic medications also have a
limited evidence base that supports their use in PTSD
• The sedatives are controversial as PTSD patients have high addiction
rates
A pharmacodynamic moment
Why do some atypical antipsychotics make good hypnotic agents?
• First, using an atypical antipsychotic to treat insomnia has risks and
benefits
– Pros
◦ Relatively fast onset
◦ Non-addictive
◦ May induce sleep onset and improve deep sleep propensity
– Cons
◦ Risk of serious side effects that other hypnotics do not have (TD,
EPS, metabolics, cataracts [interestingly, follow-up long-term
studies suggest little risk, but FDA language still suggests
diligence in monitoring here for quetiapine], QTc prolongation,
stroke in certain populations)
• Many atypical antipsychotics are antihistamines
– H1 receptor antagonism causes sedation and somnolence as a
result of lowering wakefulness center (tuberomammillary nucleus
[TMN]) activity while promoting sleep center (ventrolateral preoptic
[VLPO] area) activity
– This enhances the brain’s sleep–wake switch to favor sleep
– The faster acting and reliably absorbed atypical antipsychotics, each
with a shorter half-life, may be better suited as hypnotic agents as
they may have more dependable sleep onset and less morning
hangover effect
• Some atypical antipsychotics possess serotonin-2A (5-HT2A) receptor
antagonism
– This mechanism appears to help maintain patients in a sleeping state
by promoting more efficient and deeper sleep
– In this way, these antihistamine effects may initiate sleep
and 5-HT2A blocking effects may maintain deeper or more efficient
sleep
• At higher doses, atypical antipsychotics antagonize D2 receptors
– This mechanism is known to calm agitated patients who are
psychotic Nurs 6630 case #2 The figment of a man who looked upon the lady, Walden University
157
Downloaded from http://stahlonline.cambridge.org
by IP 192.168.60.239 on Tue Jan 02 23:33:28 GMT 2018
Stahl Online © 2018 Cambridge University Press.
All rights reserved. Not for commercial use or unauthorized distribution.
PATIENT FILE
– It is possible this calming effect lowers anxiety and cortical
hyperarousal at bedtime, allowing better sleep onset
• This profile of H1, 5-HT2A, and D2 antagonism is unique to
the atypical antipsychotics and is not found in any approved hypnotic
agent
Tired of writing those papers for your nursing classes? Use our writers to lessen your workload at school. Get the best nursing research paper right now!
• If approved hypnotic agents fail to aid in sleep initiation or maintenance
then atypical antipsychotics may be a reasonable choice
A Sleep/wake switch on and awake
B Sleep/wake switch off and asleep
cortex
cortex
HA neuron
HA neuron
GABA
neuron
GABA
neuron
ON
OFF
Sleep/wake switch
Sleep/wake switch
SCN
TMN
wake
promoter
TMN
wake
promoter
VLPO
sleep
promoter
VLPO
sleep
promoter
Overactivation
Normal
Baseline
Hypoactivation
SCN
LAT
LAT
Figure 11.1. A and B. Sleep/wake switch.
158
Downloaded from http://stahlonline.cambridge.org
by IP 192.168.60.239 on Tue Jan 02 23:33:28 GMT 2018
Stahl Online © 2018 Cambridge University Press.
All rights reserved. Not for commercial use or unauthorized distribution.
PATIENT FILE
Antihistamine and the sleep–wake switch
• The hypothalamus is a key control center for sleep and wakefulness, and
the specific circuitry that regulates sleep/wake is called the sleep/wake
switch
• The “off” setting, or sleep promoter, is localized within the VLPO of the
hypothalamus, while “on”, wake promoter, is localized within the TMN of
the hypothalamus
• Two key neurotransmitters regulate the sleep/wake switch: histamine
from the TMN and GABA from the VLPO
– When the TMN is active and histamine is released in the cortex and
into the VLPO, the wake promoter is on and the sleep promoter is
inhibited (Figure 11.1A) Nurs 6630 case #2 The figment of a man who looked upon the lady, Walden University
◦ H1 receptor antagonists, antihistamines, block this wakefulness
pathway whereby the released histamine transmitter cannot
activate frontal lobe neurocircuitry, causing a loss of arousal and
resultant fatigue
– When the VLPO is active and GABA is released into the TMN, the
sleep promoter is on and the wake promoter inhibited (Figure 11.1B)
– The sleep/wake switch is also regulated by orexin/hypocretin
neurons in the lateral hypothalamus (LAT), which stabilize
wakefulness, and by the suprachiasmatic nucleus (SCN) of the
hypothalamus, which is the body’s internal clock and is activated by
melatonin, light, and activity to promote either sleep or wakefulness
Serotonin receptor antagonism and sleep
• The 5-HT2 receptor subfamily is comprised of several types with the
three most commonly studied subtypes: 5-HT2A, 5-HT1A, and 5-HT2C
• 5-HT7 and 5-HT1D receptors have also been evaluated more recently for
their hypnotic, circadian, and antidepressant effects
• Evidence from both clinical and preclinical studies suggests that 5-HT2A
receptors modulate and improve slow wave sleep (SWS) when blocked
– This is considered deep and restorative
– Is often lacking in depressed or fibromyalgia (FM) patients
• 5-HT2A receptor antagonists may not induce hypnosis, or sleep onset,
but once sleep occurs, there is a shift toward more efficient and
improved SWS
• 5-HT2A receptor blockade may promote better sleep by a complex
mechanism
– Serotonin typically diminishes cortical glutamatergic arousing
neurons by agonizing 5-HT1A receptors and enhances glutamatergic
excitatory arousal by stimulation of 5-HT2A receptors
– In effect, antagonizing the 5-HT2A receptor dampens cortical activity
to promote some somnolence and fatigue
159
Downloaded from http://stahlonline.cambridge.org
by IP 192.168.60.239 on Tue Jan 02 23:33:28 GMT 2018
Stahl Online © 2018 Cambridge University Press.
All rights reserved. Not for commercial use or unauthorized distribution.
PATIENT FILE
– This may help maintain deeper sleep throughout the night as normal
sleep cycle arousal is lowered (See Figure 11.2)
– Currently there are several compounds (volinanserin, esmirtazapine,
pruvanserin, pimavanserin, APD125, AVE8488, HY-10275, ITI-722)
in clinical development for the treatment of insomnia that utilize this
5-HT2A receptor antagonism, at least in part, as their hypnotic
mechanism of action
raphe
GLU Nurs 6630 case #2 The figment of a man who looked upon the lady, Walden University
neuron
5HT1A glutamate brake
Mechanism of action of SARIs:
serotonin-2A antagonism potentiates inhibitory action
at serotonin-1A receptors
5HT2A glutamate accelerator
C
5HT
neurons
raphe
inhibition
of glutamate
release
5HT1A
brake:
inhibits
glutamate release
Figure 11.2. Mechanisms involved in the sleep/wake cycle.
In the image on the left, glutamate’s excitatory influence arouses the
cortex and promotes wakefulness, even at night. On the right, 5-
HT2A receptor blockade is noted and glutamate activity lowers, and
secondarily, cortical activity is dampened, resulting in deeper, more
efficient sleep with less nocturnal awakenings
What about 5-HT1D receptor antagonism?
• This autoreceptor may be stimulated by use of triptans to treat migraine
headaches
• However, as a presynaptic autoreceptor, it may be antagonized by some
antipsychotics and result in:
– Facilitated serotonin release
– Facilitated NET as a postsynaptic heteroreceptor
160
Downloaded from http://stahlonline.cambridge.org
by IP 192.168.60.239 on Tue Jan 02 23:33:28 GMT 2018
Stahl Online © 2018 Cambridge University Press.
All rights reserved. Not for commercial use or unauthorized distribution.
PATIENT FILE
– Facilitated glutamate transmission as a heteroreceptor
– Rodent preclinical models suggest this mechanism may allow for
antidepressant activity
– It is unclear if 5-HT1D promotes better sleep
– Combination 5-HT1D antagonist–SSRI antidepressants are being
researched; vortioxetine is approved and an antidepressant now
Have you hit a wall with your nursing papers? Hire one of our writers to reduce your workload. Get expert help writing a nursing paper right now.
What about 5-HT7 receptor antagonism? Nurs 6630 case #2 The figment of a man who looked upon the lady, Walden University
• This case discusses some of the complex pharmacodynamics of
quetiapine (Seroquel), but other atypical antipsychotics also have unique
pharmacodynamic profiles that may contribute to their theoretical potential
• 5-HT7 receptor antagonism is not a property highly possessed by
quetiapine (Seroquel), but is a potential novel mechanism by which other
antipsychotics may allow for antidepressant and improved sleep effects
• The atypical antipsychotics asenapine (Saphris) and lurasidone (Latuda)
possess a higher affinity for this receptor blockade, as does the classic
atypical antipsychotic clozapine (Clozaril)
• The 5-HT7 receptor seems to be sensitive to light and circadian rhythms
and may exert antidepressant potential through this complex mechanism
• Perhaps by improving sleep at night, energy and concentration during
the daytime (depressive symptoms) may improve
• For example, rodent models show antidepressant properties when this
receptor is blocked pharmacologically or removed genetically
• However, many of these effects will only occur at certain times of the
day or the night
• It is also worth noting that the SSRI antidepressants boost synaptic
serotonin levels, which ultimately causes the downregulation of these
5-HT7 receptors, and which is roughly equivalent to the blockade
provided by the atypical antipsychotics noted earlier
– The antidepressant vortioxetine has high affinity for 5-HT7 receptor
antagonism
– The atypical antipsychotic with high 5-HT7 receptor antagonism and
approval to treat bipolar depression as a monotherapy is lurasidone
(Latuda)
Posttest self-assessment question and answer
Which of the following properties of certain atypical antipsychotics lend to
their ability to promote and maintain sleep?
A. Histamine-1 receptor antagonism
B. Serotonin-2A receptor antagonism
C. Serotonin-7 receptor antagonis
D. A and B
E. All of the above
161
Downloaded from http://stahlonline.cambridge.org
by IP 192.168.60.239 on Tue Jan 02 23:33:28 GMT 2018
Stahl Online © 2018 Cambridge University Press.
All rights reserved. Not for commercial use or unauthorized distribution.
PATIENT FILE Nurs 6630 case #2 The figment of a man who looked upon the lady, Walden University
Answer: E
The antihistamine property is common to the approved hypnotic doxepin
(Silenor) and the over-the-counter sleep aid diphenhydramine (Benadryl),
and is shared by some of the atypical antipsychotics. This property helps to
initiate sleep while 5-HT2A receptor antagonism of the atypical
antipsychotics tends to maintain and promote deeper sleep. 5-HT7 receptor
antagonism appears to help circadian rhythms in order to promote
appropriate timing and length of sleep duration.
References
1. American Psychiatric Association. Treatment of Patients with Acute
Stress Disorder and Posttraumatic Stress Disorder Guidelines.
Washington, DC: American Psychiatric Association, 2004.
2. Stahl SM. Stahl’s Essential Psychopharmacology, 4th edn. New York,
NY: Cambridge University Press, 2013.
3. Stahl SM. Stahl’s Essential Psychopharmacology: The Prescriber’s
Guide, 5th edn. New York, NY: Cambridge University Press, 2014.
4. Ravindran LN, Stein MB. Pharmacotherapy of post-traumatic stress
disorder. Curr Top Behav Neurosci 2010; 2:505–25.
5. Miller LJ. Prazosin for the treatment of posttraumatic stress disorder
sleep disturbances. Pharmacotherapy 2008; 28:656–66.
6. Schwartz TL, Nihalani N. Tiagabine in anxiety disorders. Expert Opin
Pharmacother 2006; 7:1977–87.
7. Berlin HA. Antiepileptic drugs for the treatment of post-traumatic
stress disorder. Curr Psychiatry Rep 2007; 9:291–300.
8. Schwartz TL, Stahl SM. Treatment strategies for dosing the second
generation antipsychotics. CNS Neurosci Ther 2011; 17:110–17.
9. Stahl SM. Multifunctional drugs: a novel concept for
psychopharmacology. CNS Spectr 2009; 14:71–3.
10. Stahl SM. Selective histamine H1 antagonism: novel hypnotic and
pharmacologic actions challenge classical notions of antihistamines.
CNS Spectr 2008; 13:1027–38.
11. Sharpley AL, Solomon RA, Fernando AI, da Roza Davis JM, Cowen PJ.
Dose-related effects of selective 5-HT2 receptor antagonists on slow
wave sleep in humans. Psychopharmacology (Berl) 1990; 101:568–9.
12. Dugovic C,Wauquier A. 5-HT2 receptors could be primarily involved in
the regulation of slow-wave sleep in rat. Eur J Pharmacol 1987;
137:145–6. Nurs 6630 case #2 The figment of a man who looked upon the lady, Walden University
13. Teegarden BR, Al Shamma H, Xiong Y. 5-HT2A inverse-agonists for the
treatment of insomnia. Curr Top Med Chem 2008; 8:969–76.
14. 5-HT2A inverse-agonists for the treatment of insomnia. http://www
.intracellulartherapies.com/investor/2009_3_10.htm. Accessed
August 6, 2010.
162
Downloaded from http://stahlonline.cambridge.org
by IP 192.168.60.239 on Tue Jan 02 23:33:28 GMT 2018
Stahl Online © 2018 Cambridge University Press.
All rights reserved. Not for commercial use or unauthorized distribution.
PATIENT FILE
15. Abbas A, Roth B. Pimavanserin tartrate: a 5-HT2a inverse agonist with
potential for treating various neuropsychiatric disorders. Expert Opin
Pharmacother 2008; 9:3251–9.
16. Eplivanserin soothes insomnia without next morning effects.
www. clinicalpsychiatrynews.com/article/S0270-6644(08)70780-X/
fulltext. Accessed August 6, 2010.
17. Ward SE, Watson JM. Recent advances in the discovery of selective
and non-selective 5-HT1D receptor ligands. Curr Top Med Chem
2010; 10:479–92. Nurs 6630 case #2 The figment of a man who looked upon the lady, Walden University
18. Davidson JR, Brady K, Mellman TA, Stein MB, Pollack MH. The
efficacy and tolerability of tiagabine in adult patients with
post-traumatic stress disorder. J Clin Psychopharmacol 2007;
27:85–8.
19. Wang Z, Kemp DE, Chan PK, et al. Comparisons of the tolerability and
sensitivity of quetiapine-XR in the acute treatment of schizophrenia,
bipolar mania, bipolar depression, major depressive disorder, and
generalized anxiety disorder. Int J Neuropsychopharmacol 2011;
14:131–42.
20. Bauer M, El-Khalili N, Datto C, Szamosi J, Eriksson H. A pooled
analysis of two randomised, placebo-controlled studies of extended
release quetiapine fumarate adjunctive to antidepressant therapy in
patients with major depressive disorder. J Affect Disord 2010;
127:19–30.
Have you hit a wall with your nursing papers? Hire one of our writers to reduce your workload.
Sample Nursing Paper on Nurs 6630 case #2 The figment of a man who looked upon the lady; Walden University
Paper Type: Case Study
Course Level: Master
Subject Area: Nursing
# Pages: 6
Introduction
Mental health problems that occur together can generate severe symptoms that require immediate treatment. For instance, a major depressive disorder (MDD) that co-exists with post-traumatic stress disorder (PTSD) and substance use disorder (SUD) often cause insomnia in the affected patients to an extent that the victims cannot perform their daily functions as usual. Insomnia can be treated using both pharmacological and non-pharmacological agents. As Bickman, Lyon, and Wolpert (2016) explain, the ability of patients with psychiatric disorders to achieve positive health outcomes form a treatment session largely depends on the appropriate choice of interventions by the mental health professional. Similarly, a mental health professional who is delivering care to a patient with a comorbidity of different psychiatric problems as explained in the case study must choose the right interventions based on the client’s situation. Some therapeutic approaches can be used to treat quite a number of mental health problems. For instance, cognitive behavioral therapy (CBT) can be used to treat several psychiatric disorders including anxiety, PTSD, MDD, and SUDs (Harvey & Gumport, 2015). Essentially, atypical antipsychotics are antidepressants, anti-manic, hypnotic, and anxiolytic as well.
Possible Questions
Every therapeutic relationship should always begin by the development of an understanding of the patient’s situation. In order to achieve this goal, the mental health profession needs to begin every treatment session by asking questions that are related to the care process. For instance, there are three possible questions that I would ask the patient described in the scenario if she were in my office. First, I would ask the patient to state some of the thoughts that prevent her from sleeping normally at night. The rationale for asking this question is that it will help me to understand the severity of the patient’s mental condition (Harvey & Gumport, 2015). Second, I would want to know the types of drugs that the client is currently using. Asking this question will enable me to gather relevant information that will guide drug prescription (Stahl, 2014b). Third, I would ask the patient if she is experiencing any side-effects of the drugs that she is using at the moment. By asking such a question, I will be able to understand possible drug reactions and to make an informed decision as to whether some of the agents should be changed or not (Stahl, 2013). Nurs 6630 case #2 The figment of a man who looked upon the lady, Walden University
People in the Patient’s Life
People in the patient’s life are important sources of information that can be useful for her care. In the given scenario, the practitioner needs to obtain feedback from the client’s parents and close friends in order to further assess her situation. The patient’s parents and friends would be asked to give information about her behavior including her interest in daily activities, sleep pattern, and any other problematic actions. Besides, the client’s acquaintances would be asked to provide information related to drug use (Stahl, 2013). The healthcare professional can also obtain feedback from the patient’s primary clinician who has been involved in care in the previous years. The specific information that would be gathered from the incumbent concerns the client’s response to drugs and if there are any special considerations that should be made during the care process (Stahl, 2013).
Physical Exams and Diagnostic Tests
In addition to the subjective data that has been collected from the patient and the people close to her, the healthcare professional needs to gather objective data by performing physical examinations and diagnostic tests. The physical exam that would be appropriate for the clients is direct observation. By directly observing the patient’s movements, the clinician will be able to notice any changes in behavior that may help with diagnosis (Bickman, Lyon, & Wolpert, 2016). Furthermore, the attending healthcare professional should perform diagnostic tests for mental disorders using the DSM-5 manual in order to confirm the presence of disease. The American Psychiatric Association (2013) has documented several criteria that a client must meet for the diagnosis of various mental disorders to be confirmed. These criteria can be helpful in ruling out the occurrence of some conditions in the given scenario. The results of the two assessments will be used to make a ruling as to whether the patient is suffering from specific mental problems or not (Bickman, Lyon, & Wolpert, 2016).
Differential Diagnoses
The differential diagnoses for the client are the major depressive disorder (MDD), generalized anxiety disorder, or post-traumatic stress disorder (PTSD). Such a ruling has been made because the patient is currently experiencing sleep disorder which is a positive criterion in all the three conditions. According to the American Psychiatric Association (2013), clients who suffer from major depressive disorder often present with depressed mood, sleep disturbance, and an abnormal increase in body weight. Additionally, insomnia, overweight, and agitation are common symptoms in patients with a generalized anxiety disorder (Vahia, 2013). However, from the given scenario, it has been indicated that the client presents with additional symptoms including flashback and nightmare, lack of control, and panic attacks, which are positive for the post-traumatic stress disorder. Therefore, the most likely diagnosis for the client is insomnia due to post-traumatic stress disorder. Nurs 6630 case #2 The figment of a man who looked upon the lady, Walden University
Pharmacological Agents and their Dosing
The client in the given scenario can be treated using sleep/wake therapy. Based on the pharmacodynamics and pharmacokinetics of various pharmacological agents, the best medications that will help to eliminate the symptoms of post-traumatic stress disorder are a group of drugs known as atypical antipsychotics (Scarff, 2015). Examples of such drugs that can be used in the given case are Seroquel (quetiapine) and Silenor (hypnotic doxepin). The reason is that these substances have the ability to initiate and maintain sleep respectively (Stahl, 2014b). The dosage of Seroquel that would be appropriate for the patient is 25 to 50 mg at bedtime. The high Seroquel dose has been chosen because it will help to induce sleep while at the same time acting against symptoms of PTSD. The right dosage of Silenor is 3-6 mg per day administered 30 minutes before bedtime (Stahl & Grady, 2017). As Stahl (2014b) explains, the dose range for Silenor should be maintained between 3 and 6 mg per day to avoid the occurrence of serious side effects.
Rationale for choosing one Agent Over the Other
A decision to use one pharmacological agent over the other should be made based on the mechanism of action of the two drugs described above. For instance, while Seroquel is a serotonin receptor antagonist, Silenor is an antihistamine with the ability to generate the sleep-wake switch. According to Stahl (2014b), atypical antipsychotics have got specific properties that give them the ability to initiate and maintain sleep thereby helping to treat insomnia. For instance, antihistamines such as Silenor act by inducing sleep. Conversely, serotonin receptor antagonists such as Seroquel act by maintaining a deeper sleep. For insomnia to be treated effectively, a deep sleep must be initiated and maintained using appropriate medications (Stahl & Grady, 2017). Therefore, the clinician should use both Seroquel and Silenor to maximize the effectiveness of sleep-wake therapy and to completely treat insomnia.
Possible Therapeutic Changes
Follow-up assessment is important in the given scenario because it will give the clinician an opportunity to examine the patient’s progress and to make changes in the treatment process as necessary (Harvey & Gumport, 2015). If I were the attending clinician, I would not have administered paroxetine during the client’s follow-up visit nine months later. The reason is that administering bupropion and paroxetine simultaneously could potentially increase risks of seizers in case the patient was a poor CYP450 2D6 enzyme metabolizer (Stahl, 2014b). Besides, I would not have prescribed tiagabine due to the same reason. Instead, I would have administered bupropion alone as I study the patient’s progress to avoid the occurrence of seizure-related complications (Stahl, 2014b). Furthermore, I could not have administered Seroquel during the patient’s follow-up visit at 24 months because it is associated with metabolic disorders. Rather, I would have prescribed atypical psychotics which are metabolically friendly such as Saphris (Stahl, 2013; Stahl, 2014b; Stahl & Grady, 2017).
Lessons Learnt and their Implications for Nursing Practice
The given case study presents four different lessons that have great implications for nursing practice. First, from the case, nurses learn that pharmacological agents that are used to treat certain psychiatric disorders are also effective in managing symptoms of related mental health problems. This knowledge guides nurses to select the most effective drugs for clients who may be suffering from a combination of psychiatric conditions (Stahl, 2013; Stahl, 2014b; Stahl & Grady, 2017). Second, events of the case teach nurses that the effectiveness of pharmacological agents may undermine the effectiveness of other drugs which are administered simultaneously for the treatment of other health problems. Therefore, they should master drug interaction tables for accurate and correct administration of multiple drugs. Third, the presented case teaches nurses that genetic factors can prevent a drug from performing the desired functions in the patient’s body. In that regard, the practitioners should have an understanding of the pharmacodynamic and pharmacokinetic factors in a client that may impact the functions of various drugs (Stahl, 2014b; Stahl & Grady, 2017). Fourth, from the given scenario, nurses learn that atypical antipsychotics have the ability to initiate and maintain a deeper sleep with mild side effects. This knowledge guides nurses to effectively monitor and evaluate the progress of patients who have received drugs that are classified as atypical antipsychotics (Stahl, 2013; Stahl, 2014b; Stahl & Grady, 2017). Nurs 6630 case #2 The figment of a man who looked upon the lady, Walden University
Conclusion
To sum everything up, atypical antipsychotics may act as antidepressants, anti-manic, hypnotic, and anxiolytics based on their types and mechanisms of action. Mental health professionals must always remember that every therapeutic relationship should begin by the development of an understanding of the patient’s situation. Moreover, the healthcare professionals should identify people in their patient’s life who can provide information that can be useful for the care process. Following an accurate diagnosis of a mental disorder, the healthcare professional must select the right drugs and be sure to administer the correct doses for the achievement of positive patient outcomes.
References: Nurs 6630 case #2 The figment of a man who looked upon the lady paper
American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Washington, DC: Author.
Bickman, L., Lyon, A. R., & Wolpert, M. (2016). Achieving precision mental health through effective assessment, monitoring, and feedback processes. Administration and Policy in Mental Health, 43, 271-276. Doi: 10.1007/s10488-016-0718-5
Harvey, A., & Gumport, N. (2015). Evidence-based psychological treatments for mental disorders: Modifiable barriers to access and possible solutions. Behavior Research and Therapy, 68, 1-12. doi: 10.1016/j.brat.2015.02.004.
Scarff, J. R. (2015). Posttraumatic stress disorder: Think beyond prazosin when treating nightmares in PTSD. Current Psychiatry, 14(12), 56–57. Retrieved from http://www.currentpsychiatry.com/specialty-focus/posttraumatic-stress-disorder/article/think-beyond-prazosin-when-treating-nightmares-in-ptsd/09d61c8717ad9887080f0a1d92cf6c5b.html
Stahl, S. M. (2013). Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications (4th ed.). New York, NY: Cambridge University Press.
Stahl, S. M. (2014b). The prescriber’s guide (5th ed.). New York, NY: Cambridge University Press.
Stahl, S. & Grady, M. (2017). Stahl’s essential psychopharmacology: Prescriber’s guide. Cambridge, United Kingdom New York, NY: Cambridge University Press.
Vahia, V. N. (2013). Diagnostic and statistical manual of mental disorders 5: A quick glance. Indian journal of psychiatry, 55(3), 220.
