Pretest self-assessment question (answer at the end of the case)
What is the evidence to support the use of clonazepam (Klonopin) in manic patients?
A. It is not approved but meta-analysis studies show effectiveness
B. It is not approved but small-scale studies show effectiveness
C. It is not approved but case series and case studies show effectiveness
D. It is approved, based on large-scale regulatory studies
E. A, B, and C
Patient evaluation on intake
35-year-old woman with a chief complaint of difficulty coping at her job
Psychiatric history
The patient has had psychiatric symptoms since her 20s. She reports depression and agitation as her predominant, albeit fluctuating symptoms
States that she has alienated friends and co-workers by being verbally intrusive at times
Cannot complete work assignments and feels depressed
Admits full MDD symptoms now but is not suicidal
Simultaneously is agitated, has rapid speech, intrusive behaviors, condescending demeanor, distractibility, and appears thought disorganized with blocking
States that she also suffers interruptions
– These are described initially as her own thoughts taking over her brain, or as her own thoughts making their own comments to her, but never defined as other voices or hallucinations. These events cause her thought blocking
History includes at least two psychiatric hospitalizations for depression She has had no suicide attempts
– A review of psychiatric systems revealed no formal anxiety disorder, eating disorder, SUD over the last decade. She states the only addictive drugs she has used are those provided by her previous psychiatrist (d/l-mixed amphetamine salts [Adderall])
– Attended eclectic, supportive psychotherapy in the past but has not had formal CBT or PDP
– There is no evidence of marked personality disorder
– Patient states that she suffers from ADHD per her previous prescriber and has utilized stimulants more recently as a result. Her inability to focus right now is a main concern as she cannot get tasks completed
– Presents with no medications as her previous psychiatrist has terminated with her
– Previously failed to respond to adequately dosed SSRIs (escitalopram [Lexapro] 30 mg/d, fluoxetine [Prozac] 40 mg/d, paroxetine [Paxil] 40 mg/d) and SNRIs (venlafaxine-XR [Effexor-XR] 300 mg/d) in the past
– Responded to typical antipsychotics (thiothixene [Navane] 40 mg/d, haloperidol [Haldol] 10–20 mg/d), and atypical antipsychotics (risperidone [Risperdal] 4 mg/d), but has had abnormal movements, which she states were TD, as a result
– Has responded to divalproex sodium (Depakote) 1500 mg/d but developed elevated ammonia levels with an altered mental state
– Lamotrigine (Lamictal) was not therapeutic as she developed a non-serious rash at low doses and had to discontinue it
– Most recently has been taking mixed amphetamine salts (Adderall) 50 mg/d and subsequently lisdexamfetamine (Vyvanse) 60 mg/d in order to improve energy, concentration, and focus, but has run out of medications between providers
Social and personal history
Married and has no children
Is college educated, works as a social worker at a local hospital
Does not drink alcohol, smoke cigarettes, or take illegal drugs
Medical history
Asthma
Migraines
Possible history of drug-induced dyskinesia
Family history
None
Current psychiatric medications
None as she has been off her stimulant and SSRI for two weeks
Current medical medications
None
Question
Based on what you know about this patient’s history and current symptoms, what would you consider her working diagnosis to be?
Psychotic MDD
Bipolar mania
Bipolar or MDD with mixed features
Stimulant intoxication
Borderline personality
What would you do first?
Obtain information from previous provider
Obtain information from previous inpatient stays
Obtain information from her pharmacy regarding medications filled to better assess the completeness of her medication trials and to corroborate her fragmented history
Add an antidepressant
Add lithium or divalproex sodium (Depakote) or carbamazepine (Equetro)
Add an atypical antipsychotic
Attending physician’s mental notes: initial evaluation
Patient is 100% dysphoric overall, appears to be distraught, agitated, and has some subsyndromal manic symptoms and psychotic thought disorder (versus hallucinations)
– Per DSM-5, once psychosis occurs, the patient is declared fully manic and a bipolar 1
– Per new entity in DSM-5, this could be a (if bipolarity is being considered) “with mixed features specifiers” scenario
This specifier may occur in bipolar or MDD patients
In this case, three MANIA criteria must be met in presence of MDD
Obtaining an accurate history is difficult given her mental state
Could be an agitated depression, mixed features, borderline personality or stimulant intoxication
Key is initially to confirm with her family that patient is safe to be at home, given her lability and thought disorder
Then will need to corroborate her history by obtaining records
Patient also reports she has had marked side effects
Will need to consider these symptoms as possibly hypochondriacal, legitimate, or that patient has a p450 isoenzyme deficiency causing marked side effects
She is on no medications now; she ideally needs a monotherapy with low side effects, benign p450 isoenzyme profile, with inherent ability to treat depression/mania, mixed features, and psychosis all in one
In case this is bipolar mixed features, unipolar mixed features, or iatrogenic escalated mania, her stimulants and antidepressants likely should be avoided and not restarted
Further investigation
Is there anything else you would especially like to know about this patient?
What is her longitudinal history?
– She has been gainfully employed
– She is intelligent
– She is successfully married with a supportive spouse
– She has clear exacerbations of her psychiatric symptoms and has required inpatient stays but apparently without suicidal ideas, intentions, or attempts
– She appears to function well with inter-episode recovery
– Almost every medication has caused side effects
– Her exacerbation currently seems to involve increased irritability, intact self-esteem, and thought disorder, which is a novel presentation per the patient
– She states typically she would be depressed with agitation and insomnia, but not with these possible psychotic features, which are alarming to her and a novel presentation
Attending physician’s mental notes: initial evaluation (continued)
The patient is clearly distressed and is overly focused on improving her ability to concentrate and function better
Stimulants increase the DA/NE activity of her brain and could make her lability or thought disorder worse
At the initial session, it is impossible to obtain old records and a decision to mitigate symptoms has to be made now
She appears to have mixed features and is minimally psychotic, although it is possible these have been iatrogenically started by use of stimulants without an appropriate mood stabilizer in place
As she has had difficulty on most medications and this history is sparse and complicated, a trial of an atypical antipsychotic is best positioned to cover all clinical scenarios: psychosis, mania, mixed features, agitation, intoxication, depression, and should avoid any further manic escalation
A mood stabilizer (carbamazepine[Equetro] or divalproex[Depakote]) will not cover psychosis or help her depression
Lithium cannot easily be loaded and utilized quickly due to toxicity and a narrow therapeutic window
Adding a stimulant may cause psychosis
Adding an antidepressant may cause more mixed–manic features
Choice of medication should include an agent that requires little CYP450 hepatic metabolism
The patient does not wish to gain weight
Case outcome: interim follow-ups through one month
The patient is seen weekly because of her symptoms
– Records are requested but do not arrive
– Several medications are presented and the patient states she has a negative tolerability history with many of them
– States divalproex sodium (Depakote) has worked well but she fears re-emergence of hyperammonemia
– Feels that risperidone (Risperdal) was helpful too but caused weight gain and movement disorder
After the following informed consent she agrees to a trial of paliperidone (Invega)
– Is the atypical in the class that least requires p450 metabolism
– Is primarily renally excreted
– Can be titrated easily to allow adequate monitoring and treatment of emergent extrapyramidal symptoms
– She is at risk for TD again, but this can be monitored closely and removed if needed
– Has 52 weeks of data showing minimal metabolic impact
– It is approved to treat schizophrenia but its D2 receptor antagonism might alleviate mania and mixed features
Paliperidone (Invega) 3 mg/d is initiated, which is subtherapeutic but should limit adverse effects initially. On day 4, the patient states she has more insomnia and dysphoric lability post dose, but is better able to focus and concentrate during the daytime
Dosed next at 6 mg/d, which is not tolerated due to agitation and gastrointestinal (GI) issues. There were no EPS side effects, however
Patient states that the typical antipsychotic thiothixene (Navane) had helped at one hospitalization and asked to try this instead, and it was dosed now at 5–10 mg/d
Now allowed to take diphenhydramine (Benadryl) 50 mg for insomnia or emergent EPS as needed
Considering her current use of a typical antipsychotic, what clinical monitoring would you suggest?
Routine monitoring for treatment-emergent TD/EPS is needed as she reports a history of movement disorder, which appears to include dystonias and dyskinesias involving tic-like features
– Consider AIMS testing frequently
– Provide clear informed consent regarding emergence of TD and its possible permanence
Is routine measurement of weight, abdominal girth, blood pressure, blood lipids, and glucose warranted due to metabolic risks?
– The typical antipsychotics do not carry metabolic risk warnings like the atypical antipsychotics
– Thiothixene (Navane) and other high-potency typicals are not clinically well documented to cause AAWG; therefore, this type of monitoring may not be necessary
– If lower-potency typicals (chlorpromazine [Thorazine], thioridazine [Mellaril]) are to be used, they clearly promote weight gain and likely metabolic disorder, and monitoring similar to that utilized during atypical antipsychotic use should occur
If records can be obtained and if her EPS
– Appear more dystonic, then prophylactic use of anticholinergics (diphenhydramine [Benadryl], benztropine [Cogentin]) are warranted
– Appear more akathisia-based, then as needed-or even prophylactic beta-blocker or BZ use may be warranted
This patient has a tenuous history of tolerating medications
– Being diligent about side, effect monitoring is worthwhile clinically
– Utilizing antidotes for side effects is imperative
– Additionally, being patient and supportive with numerous complaints may be good for rapport building, medication compliance, and ultimately allow better outcomes due to the ability to obtain better dosing
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