Discussion: Sleep/Wake Disorders

Discussion: Sleep/Wake Disorders

Discussion: Sleep/Wake Disorders

It is not uncommon to experience a night or two of disrupted sleep when there is something major going on in your life. However, sleep/wake disorders are much more than an occasional night of disrupted sleep. A recent report from the Centers for Disease Control and Prevention estimated that between 50 and 70 million American have problems with sleep/wake disorders (CDC, 2015). Although the vast majority of Americans will visit their primary care provider for treatment of these disorders, many providers will refer patients for further evaluation. For this Discussion, you consider how you might assess and treat the individuals based on the provided client factors.

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Learning Objectives

Students will:

• Assess client factors and history to develop personalized therapy plans for clients with sleep/wake disorders
• Analyze factors that influence pharmacokinetic and pharmacodynamic processes in clients requiring therapy for sleep/wake disorders
• Evaluate efficacy of treatment plans for clients presenting for sleep/wake therapy
• Apply knowledge of providing care to adult and geriatric clients presenting for sleep/wake disorders

Learning Resources

Note: To access this week’s required library resources, please click on the link to the Course Readings List, found in the Course Materials section of your Syllabus.

Required Readings

Note: All Stahl resources can be accessed through the Walden Library using this link. This link will take you to a log-in page for the Walden Library. Once you log into the library, the Stahl website will appear.

Stahl, S. M. (2013). Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications (4th ed.). New York, NY: Cambridge University Press.

To access the following chapters, click on the Essential Psychopharmacology, 4th ed tab on the Stahl Online website and select the appropriate chapter. Be sure to read all sections on the left navigation bar for each chapter.

• Chapter 11, “Disorders of Sleep and Wakefulness and Their Treatment”

Stahl, S. M. (2014b). The prescriber’s guide (5th ed.). New York, NY: Cambridge University Press.

• trazodone
• triazolam
• trimipramine
• zaleplon
• zolpidem

American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Washington, DC: Author.

Note: Retrieved from Walden Library databases.

Davidson, J. (2016). Pharmacotherapy of post-traumatic stress disorder: Going beyond the guidelines. British Journal of Psychiatry, 2(6), e16-e18. doi:10.1192/bjpo.bp.116.003707. Retrieved from http://bjpo.rcpsych.org/content/2/6/e16

To prepare for this Discussion: Sleep/Wake Disorders:

Note: By Day 1 of this week, your Instructor will have assigned you to one of the following case studies to review for this Discussion. To access the following case studies, click on the Case Studies tab on the Stahl Online website and select the appropriate volume and case number.

Case 1: Volume 2, Case #16: The woman who liked late-night TV

Case 2: Volume 2, Case #11: The figment of a man who looked upon the lady

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 diagnoses 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 Guideand 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!

By Day 3

Post a response to the following:

• Provide the case number in the subject line of the Discussion.
• 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.
• Identify people in the patient’s life you would need to speak to or get feedback from to further assess the patient’s situation. Include specific questions you might ask these people and why.
• Explain what physical exams and diagnostic tests would be appropriate for the patient and how the results would be used.
• List three differential diagnoses for the patient. Identify the one that you think is most likely and explain why.
• List two pharmacologic agents and their dosing that would be appropriate for the patient’s sleep/wake therapy based on pharmacokinetics and pharmacodynamics. From a mechanism of action perspective, provide a rationale for why you might choose one agent over the other.
• 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.
• 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.

	•   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)

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	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

Discussion: Sleep/Wake Disorders

	•  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

Discussion: Sleep/Wake Disorders

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	•   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? •   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

Discussion: Sleep/Wake Disorders

	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

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PATIENT FILE

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 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

Discussion: Sleep/Wake Disorders

	–      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 •   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

Discussion: Sleep/Wake Disorders

	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 first- line 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
	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

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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

Discussion: Sleep/Wake Disorders

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

Discussion: Sleep/Wake Disorders

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

• If approved hypnotic agents fail to aid in sleep initiation or maintenance then atypical antipsychotics may be a reasonable choice

• Sleep/wake switch on and awake

cortex

HA neuron

LAT

TMN

wake promoter

GABA

neuron

VLPO

sleep promoter

SCN

Sleep/wake switch

Discussion: Sleep/Wake Disorders

• Sleep/wake switch off and asleep

	cortex
HA neuron	LAT
TMN wake	GABA	VLPO sleep
promoter	neuron	promoter
	SCN

OFF

Sleep/wake switch

Figure 11.1. A and B. Sleep/wake switch.

Discussion: Sleep/Wake Disorders

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)

• H1 receptor antagonists, antihistamines, block this wakefulnesspathway 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 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

Discussion: Sleep/Wake Disorders

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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

What about 5-HT7 receptor antagonism?

• 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)

Discussion: Sleep/Wake Disorders References

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