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
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
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
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
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
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
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”
Clinically, what types of patients typically suffer hypnagogic hallucinations?
Case outcome: interim follow-ups through 12 months (continued)
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
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