Pretest self-assessment question (answer at the end of the case)
Which of the following is true regarding QTc prolongation and antipsychotics?
A. Thioridazine (Mellaril) has a warning
B. Ziprasidone (Geodon) has a warning
C. Iloperidone (Fanapt) has a warning
D. Electrocardiogram (EKG) monitoring should occur in cardiac risk patients, or those on antipsychotic polypharmacy, or those on super-dosed monotherapies
E. Only the antipsychotics in A, B, C should have EKG monitoring
F. All antipsychotics should have EKG monitoring
G. B and C
H. A, B, C, and D
Patient evaluation on intake
42-year-old man with a chief complaint of depression and family stress
Psychiatric history
Was doing well until he became stressed with household issues and family issues
Remains gainfully employed as an assembly line worker despite his stress
When seen by a previous provider, was diagnosed with minor depression/adjustment disorder and placed on a minimal dose trial of an SSRI
Goes to weekly supportive psychotherapy
His psychiatrist moved and he presented for admission with minor depressive symptoms as noted
However, this initial psychiatric interview revealed poor sleep, irritable and low mood, poor concentration, affect constriction, loss of speech prosody, and concrete thoughts
Furthermore, when asked about psychotic symptoms, the patient nonchalantly stated that he did in fact receive messages from the TV, radio, and the assembly line at work. He admitted to “picking things up” all the time
Outside picking up messages from the TV
– If a car drove by, he could hear people talking in the car even if they were miles away
– He would also pick up images in mirrors
– These took the form of hallucinations with which he has interacted
– The messages he received from these were mostly neutral and not affective laden, although some are derogatory
– These have been present for at least a year
– He is not distressed over these occurrences
Currently takes only an SSRI from the previous provider
No other previous medication trials
No psychiatric admission history
No suicide attempts
Social and personal history
Married and has four adult children
High school educated and is working full time
Has a supportive wife, but they have had difficulties in the past
Does not drink alcohol, smoke cigarettes, or abuse drugs
There are no legal issues and he gets along well in the community and at work
Medical history
There are no acute and no chronic medical problems
Normal with regard to height, weight, and vitals
There are no abnormal movements
Family history
MDD in mother
SUD throughout extended family
ADHD in grandson
Current psychiatric medications
Sertraline (Zoloft) 50 mg/d (SSRI)
Current medical medications
None
Question
Based on this patient’s history and the available evidence, what do you consider his diagnosis to be?
What would your next treatment likely be?
Increase the SSRI, as sometimes this alleviates depressive psychosis
Add an atypical antipsychotic
Switch to an atypical antipsychotic
Better delineate his diagnosis
Refer for CBT or family therapy
Attending physician’s mental notes: initial evaluation
This patient is psychotic, which was apparently missed by the previous providers
He is not guarded. Perhaps this was missed as he appears normal to most people, has a family, is gainfully employed, is older, and does not “look schizophrenic”
Perhaps these symptoms have started in last few months and these did not exist when he started treatment with the prior provider
Perhaps these symptoms have been present for several years regardless of his stress and depression levels and he has learned to live with them
His depression is mild at best and does not appear severe enough to fuel psychotic symptoms
Will need to see if he is psychotic even when fully euthymic, which suggests the differential diagnosis of schizoaffective disorder versus schizophrenia
Will need to rule out substance-induced psychosis, although his history suggests no drug abuse
Will need to rule out medically induced psychosis as he is a bit older with regard to developing schizophrenia
Further investigation
Is there anything else you would especially like to know about this patient?
His history does need further clarification
– Family members eventually present with the patient and confirm his history
They have seen the patient stressed and depressed but never to the degree where he missed work
They have not witnessed overt psychotic behavior where he has been seen interacting with his hallucinations (although he was moved from one assembly line to another the previous year). Patient confirms he asked to move as the hallucinations were distracting
They deny that he abuses drugs or alcohol
They deny any previous family history consistent with an SPMI
The family reports that the patient has been more concrete and less emotional over the years. His loss of facial expression and bland speech has been felt to be due to depression. The patient does not see himself as depressed
The patient states that he has had these hallucinations for some time but has not recognized them as foreign. They occur regardless of mood
Medical workup shows no laboratory test abnormalities and his physical and neurological examination is normal
Question
Based on what you know about this patient’s history and current symptoms, what would you do now?
Increase the SSRI as sometimes this alleviates depressive psychosis
Add an atypical antipsychotic
Switch to an atypical antipsychotic
Better delineate his diagnosis
Order neuroimaging such as a brain MRI or computerized tomography (CT)
Order an electroencephalogram (EEG)
Order psychological testing
Refer for CBT or family therapy
Attending physician’s mental notes: initial evaluation (continued)
The patient is consistently psychotic now. He has negative symptoms that were prodromal, and this appears to be late-onset schizophrenia
Medical workup is negative
He should have brain imaging to prove he has no mass lesion, given the late-age onset of symptoms
There are no neurological changes, confusion, altered states of consciousness (delirium), and no seizure activity, thus an EEG is not warranted
He is clearly psychotic; therefore, psychological testing is not warranted
Case outcome: interim follow-ups through six months
The patient is started and titrated slowly onto risperidone (Risperdal) without issue, and is left on 4 mg/d for several weeks
This is partially effective in treating his positive symptoms. Dose is escalated to 6 mg/d
The hallucinations resolve and the mild negative symptoms continue. He continues to work without any issues
Toward the end of this period, his ideas of reference (IOR) begin to return
– Higher dosing (8 mg/d) causes mild parkinsonism-like extrapyramidal symptoms, noted as resting tremor in one arm/hand
Next he is switched to the only other atypical antipsychotic, olanzapine (Zyprexa), available at the time and is titrated to the recommended 10 mg/d, which alleviates his psychosis
Psychosis returns after several more weeks
– The atypical antipsychotic is increased to the maximum approved dose of 20 mg/d with resolution of the positive symptoms
Again psychosis returns; olanzapine (Zyprexa) is increased above the approved norm to 30 mg/d
– Positive symptoms resolve. He remains psychosis free for many months and continues to work
– 15 lbs of AAWG occurs and there is a recurrence of mild parkinsonism. He tolerates both of these side effects without immediate concern
Brain MRI is negative
Considering his current medication side effects, do you have any concerns?
The weight gain might coexist with a metabolic disorder and laboratory samples should be sent for analysis
The EPS is mild and tolerated, but he should be offered antiparkinsonian medication
This early EPS is a poor prognostic indicator and TD is more likely to develop
Need to make sure to monitor EPS closely and frequently
Given the difficulty managing his psychosis and his initial propensity to side effects, a referral for family therapy may be warranted to keep his stress levels and expressed emotion levels in the home low
Attending physician’s mental notes: six months
At the time of this treatment, metabolic disorder was not well understood or appreciated, guidelines did not exist, and laboratory blood samples were not drawn for monitoring very often
Initially, this patient looked easy to treat as his initial atypical antipsychotic was effective at usual dosing guidelines
Now, he is looking more treatment resistant as his second atypical antipsychotic is requiring very high doses to alleviate his psychosis
Olanzapine (Zyprexa) was approved at doses up to 20 mg/d
What were the causes of his relapses on risperidone (Risperdal) and lower dose olanzapine (Zyprexa)?
– Treatment resistance and his more severe illness
– An artifact of switching his medications and a window of undertreated psychosis during the cross-titration when both atypical antipsychotic doses were relatively low
He is being very compliant despite weight gain and EPS side effects
Will need to convince him to stay on his medications over the long term to avoid a worsening prognosis and social downward drift
Case outcome: interim follow-ups through nine months
Case outcome: interim follow-ups through 18 months
Continues to see his supportive psychotherapist, who also intervenes more with family in sessions aimed at decreasing household stress and high expressed emotions
Olanzapine (Zyprexa) 30 mg/d is continued
– At the time of this treatment, metabolic disorder was not well understood, guidelines were not available, and laboratory blood samples were not analyzed, but his weight was followed sequentially. His weight gain did not progress past 15 lbs
He continued to do well with only mild negative symptoms
Attending physician’s mental notes: through 20 months
Patient is doing very well
Have to continue his simple medication regimen as long as possible
It appears we began treatment in his first psychotic break
His prognosis is promising
Question
How long should you treat this patient with his antipsychotic?
After remission of psychosis, treat one year and then discontinue
After remission of psychosis, treat five years and then discontinue
After remission of psychosis, treat 10 years and then discontinue
After remission of psychosis, treat indefinitely as only 10% of schizophrenics go on to maintain remission without medications and to lead relatively normal lives
After remission of psychosis, treat indefinitely unless side effects complicate ongoing treatment
Case outcome: interim follow-ups through 24 months
The patient gradually presents with difficulties
– Increased stress due to issues with his family
– Now has insomnia
– He is not depressed, nor suicidal
– Starts to have problems at work, which require intervention and moving to yet another assembly line
– In session, he admits his psychosis is back to a moderate level. His hallucinations are mostly neutral but more now have negative and critical content
– Mild IOR are back and they may be delusional, as he feels a local company’s work trucks are following him around (this regional company has thousands of service trucks randomly around at any given time)
Question
What would you do now?
Superdose the olanzapine (Zyprexa) up to 40 mg/d to recapture efficacy
Add a typical antipsychotic as a combination therapy
Switch to a new atypical antipsychotic
Switch to a typical antipsychotic monotherapy
Attending physician’s mental notes: 24-month follow-ups
Life stress likely has caused his recurrence
Need to make sure psychotherapy is in place and need to discuss with his work how to keep him employed without losing his job. Consider disability
40 mg/d of olanzapine (Zyprexa) seems high, but he did very well for many months on the 30 mg/d dose, and could temporarily use a higher dose until psychosis subsides
Switching to the other, then currently available, a typical antipsychotic, quetiapine (Seroquel), is possible, but the cross-titration and its lower affinity may allow for more breakthrough psychosis to evolve
Clozapine (Clozaril) is an option but perhaps his schizophrenia is not sufficiently resistant yet to require clozapine and its excessive side-effect burden
Does psychotherapy treat schizophrenia?
The patient is getting supportive, intermittent family interventions but not formal family therapy in an ongoing manner. This type of therapy has an evidence base for treating schizophrenia
CBT also has data to support its use in schizophrenia, more so for improving cognition and executive functioning
Unfortunately, he likely needs more medication to lower his positive symptoms over the acute period to save his job in the short term
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