References

1. Stahl SM, Antidepressants, in Stahl’s Essential Psychopharmacology, 3rd edition, Cambridge University Press, New York, 2008, pp 511–6662. Stahl SM, Bupropion, in Stahl’s Essential Psychopharmacology The Prescriber’s Guide, 3rd edition, Cambridge University Press, New York, 2009, pp 57–62

Patient FileThe Case: The computer analyst who thought the government would choke him to death

The Question: Can you tell the difference between schizophrenia, delusional disorder and obsessive compulsive disorder?

The Dilemma: What do you do when antipsychotics do not help delusions?

Pretest Self Assessment Question(answer at the end of the case) Which disorder(s) listed below have hallucinations associated with them?

A. OCD

B. Delusional disorder

C. Schizophrenia

D. Simple schizophrenia

E. Schizotypal personality disorder

Patient Intake 38-year-old man referred for evaluation of his chief complaint that “the government is out to get me and there is a grand conspiracy against me”

Psychiatric History Uneventful childhood but became “suspicious” with some strange thoughts and sexual ideas diagnosed as OCD and for which he retained insight that they were excessive and not true

He would look at people in the face and develop disturbing sexual thoughts, so began to avoid eye contact

Given SSRIs with equivocal improvement

Some affective instability variably diagnosed as bipolar disorder or schizoaffective disorder

Main treatment was psychotherapy between ages 19 and 27 which the patient believes helped him greatly “hold things together”

After college, got a job as a computer analyst for the government, but quit precipitously a few months ago after he began to think that the government was against him and they would “do him in” by which he thought he would be choked to death

Is currently preoccupied by police cars, thinking they are after him

He now regrets resigning from his job but has no doubt that the government is actually after him, even though he admits no one else, including his wife, believes this

Affect somewhat flat but not overtly depressed

No other delusions, no hallucinations and no thought disorder

Social and Personal History College graduate

Successful computer analyst for 15 years

Married

No children

No drug or alcohol abuse

Medical History Obese

Smoker

Family History Sister: schizophrenia

Paternal aunt: schizophrenia

Current Medications Topiramate (Topamax) 300 mg/day

Buproprion SR (Wellbutrin SR) 300 mg/day

Buspirone (Buspar) 60 mg/day

Paroxetine (Paxil, Seroxat) 60 mg/day

Aripiprazole (Abilify) 40 mg/day

Risperidone (Risperdal) 8 mg/day

What do you think is his diagnosis?

OCD

Paranoid schizophrenia

Schizoaffective disorder

Delusional disorder

Simple schizophrenia

Schizophreniform disorder

Schizotypal personality disorder

Obsessive compulsive personality disorder

Schizoid personality disorder

Attending Physician’s Mental Notes: Initial Psychiatric Evaluation Seems like early OCD evolving into paranoia, but of a delusional nature, not of a paranoid schizophrenia nature

Does not seem like simple schizophrenia– Even though no hallucinations present– Not much functional decline yet– Also, this is an ICD10 and not a DSM IV concept– However, the patient is still young and if his symptoms progress, simple schizophrenia might be a future diagnostic consideration

Since he has delusions, this is not schizotypal personality disorder– However, he may have had some premorbid schizotypal features with his early OCD symptoms, such as unusual perceptual experience, odd thinking, suspiciousness, lack of many close friends and excessive social anxiety

How would you treat him?

Try another SSRI

Try another atypical antipsychotic

Raise the dose further of his current SSRI

Raise the doses further of his current antipsychotics

Reduce the doses of his antipsychotics

Discontinue one of his antipsychotics

Refer for psychotherapy

Attending Physician’s Mental Notes: Initial Psychiatric Evaluation, Continued He seems excessively medicated, probably in an attempt to get better control of his delusion about the government, but obviously without much benefit– Should his medications be decreased?– Should he try heroic doses of different medications?

Decided to recommend discontinuation of both bupropion SR and paroxetine, cross tapering them with fluvoxamine, an agent with sigma 1 properties reported to work both in OCD and in delusional/psychotic depression

For now, leave other medications alone

Case Outcome: First Interim Followup, Week 12 His local psychiatrist switched his bupropion and paroxetine to fluvoxamine 200 mg/day without notable changes in symptoms

Attending Physician’s Mental Notes: First Interim Followup, Week 12 Sometimes responses to SSRIs are slow, so plan to keep with fluvoxamine for a few more months

The question is whether to reduce his antipsychotics, or switch him to another heroic dosing trial with another antipsychotic

Since aripiprazole has higher affinity for D2 dopamine receptors than risperidone, and is only a partial agonist, it can theoretically interfere with the actions of risperidone

The first thing to try is to reduce aripiprazole and maintain risperidone and see if, despite lowering the total dose of the two antipsychotics, that he might actually show improvement

If this does not work, there are anecdotal reports, but very little data, that some patients with schizophrenia seem to respond to very high doses of olanzapine or quetiapine, so maybe that is worth a try even though there is essentially no evidence of the results of this approach in patients with delusional disorder

Case Outcome: Second Interim Followup, Week 24 His local psychiatrist stopped his aripiprazole (it takes a few weeks to wash out aripiprazole since it has a 2 to 3 day half life with an active metabolite with a similarly long half life), and his doctor tapered it down although aripiprazole tapers itself and can be stopped at once

Amazingly, the patient seems somewhat better, but not dramatically so

Opted to continue to observe, possibly increase his fluvoxamine while keeping risperidone dose stable and see if there is further improvement over the next few months

Case Debrief This patient was a first degree relative of two family members with schizophrenia

His disorder is consistent with being related to schizophrenia, as a lower severity and later onset condition such as delusional disorder

However, some epidemiological studies suggest that delusional disorder may not be increased in family members of patients with schizophrenia

If the patient has some odd thoughts that he knows are false (i.e., obsessions) and other odd thoughts that only he thinks are true (i.e., delusions), it is possible that he has evolved from a case of OCD, perhaps with some schizotypal personality features, into a case of comorbid delusional disorder plus OCD that may be on the way to becoming a case of simple schizophrenia

Delusional disorder typically has onset around age 40, whereas schizophrenia generally starts much earlier

Delusional disorder can be impervious not only to reason, but also to antipsychotics

Combination of aripiprazole with other psychotics such as risperidone can actually reduce the efficacy of risperidone since aripiprazole successfully competes for D2 receptors with risperidone

Performance in Practice: Confessions of a Psychopharmacologist What could have been done better here?– Should neuropsychological testing have been done in his teens and then repeated more recently as additional symptoms evolved?– Should he get neuropsychological testing now as a baseline in case his condition evolves further with cognitive decline, to document his current functioning and have a potential quantitative assessment of cognitive functioning for comparison in the future?

Possible action items for improvement in practice– Did he evolve into too high dosing and too many drugs in a desperate attempt to help him?– Sometimes it is better to accept the limits of the drugs, especially antipsychotics, and not overtreat because this may generate more side effects in the long run than justified by meager therapeutic effects– Psychotherapy has helped this patient in the past, and rather than challenge his delusion, use psychotherapy to help him learn not to talk about this delusion at work or in social settings so it does not compromise potential future employment or friends

Two-Minute Tute: A brief lesson and psychopharmacology tutorial (tute) with relevant background material for this case – Differential diagnosis of delusional disorder

Delusional disorder according to DSM IV and ICD 10 Nonbizarre delusions

Patients do not have simultaneous hallucinations, disorganized speech, negative symptoms

Functioning is not markedly impaired

Behavior not obviously odd or bizarre

if mood disorder has occurred, episodes are brief compared to duration of delusions

Not due to a substance

Delusional Disorder Mean age of onset 40 years

Rare (schizophrenia prevalence 1%; delusional disorder 0.03%)

Kendler (1985) found no increased incidence of schizophrenia or schizoid-schizotypal personality disorder in first degree relatives of delusional disorder patients, unlike this patient and his family

Persecutory type which this patient has, is the most common type (other types are erotomanic, grandiose, jealous, and somatic)

Delusions are systematized, coherent and defended with clear logic, in contrast to many persecutory delusions of schizophrenia

Patients with OCD show varying degree of insight into their obsessions and compulsions; if reality testing is lost and conviction in their beliefs reaches the level of delusions, both disorders may be present

Psychopharmacological myth is that the antipsychotic pimozide may be more effective than other treatments, but this has not held up to further studies, and pimozide has enhanced cardiovascular risks from drug interactions and overdose compared to other antipsychotics

Simple Schizophrenia A concept in ICD10 used in Europe and other parts of the world, but not a concept in DSM IV and not used as a concept as much in the United States

An uncommon disorder

Insidious but progressive onset of oddities of conduct, inability to meet the demands of society and decline in total performance

Delusions and hallucinations not evident

Negative symptoms of schizophrenia develop without being preceded by any overt psychotic symptoms

With increasing social impoverishment, vagrancy may ensue and the individual become self absorbed, idle and aimless

Schizotypal Personality Disorder May be the DSM equivalent of simple schizophrenia, except simple schizophrenia is generally progressive

Pervasive social and interpersonal deficits

Reduced capacity for close relationships

Cognitive or perceptual distortions, eccentricities of behavior beginning by early adulthood

Ideas of reference

Odd beliefs, magical thinking

Inconsistent with subcultural norms (superstitious, clairvoyant, telepathic)

Unusual perceptual experiences

Odd thinking and speech (vague, circumstantial, metaphorical, overelaborate or stereotyped)

Suspicious or paranoid ideation

Inappropriate or constricted affect

Odd, eccentric, peculiar behavior

Lack of close friends or confidants

Excessive social anxiety

Posttest Self Assessment Question: Answer Which disorder(s) listed below have hallucinations associated with them?

A. OCD

– No hallucinations

B. Delusional disorder

– No hallucinations

C. Schizophrenia

– According to either ICD10, DSM-IV or both, this is the only one of these five diagnoses with hallucinations

D. Simple schizophrenia

– No hallucinations

E. Schizotypal personality disorder

– No hallucinations

Answer: C