1. Prof. Hani Hamed Dessoki
Prof. of Psychiatry
Beni Suef University
2015
2. IntroductionIntroduction
Psychiatric comorbidities are commonPsychiatric comorbidities are common
among patients with schizophreniaamong patients with schizophrenia..
Substance abuse comorbiditySubstance abuse comorbidity
predominatespredominates..
Anxiety and depressive symptoms are alsoAnxiety and depressive symptoms are also
very common throughout the course ofvery common throughout the course of
illness, with an estimated prevalence ofillness, with an estimated prevalence of
15% for panic disorder15% for panic disorder,, 29% for29% for
posttraumatic stress disorderposttraumatic stress disorder, and, and 23%23%
for obsessivefor obsessive--compulsive disordercompulsive disorder..
3. IntroductionIntroduction
It is estimated that comorbidIt is estimated that comorbid
depression occurs in 50% ofdepression occurs in 50% of
patients, and perhapspatients, and perhaps
(conservatively) 47% of patients also(conservatively) 47% of patients also
have a lifetime diagnosis of comorbidhave a lifetime diagnosis of comorbid
substance abuse.substance abuse.
4. IntroductionIntroduction
Comorbid conditions, including obsessive-compulsive
behavior, depression, suicide, substance abuse,
aggressive behavior, and impairment of cognitive
function, reflect on prognosis of both acute as well
chronic schizophrenia.
Schizophrenia with special conditions.Schizophrenia with special conditions.
5. Management of Obsessive-CompulsiveManagement of Obsessive-Compulsive
SchizophreniaSchizophrenia
Obsessive-compulsive symptoms are often recognized
in a prodromal stage in patients with schizophrenia,
and it is often difficult to cure with standard treatment.
It has been a long controversy whether obsessive-
compulsive schizophrenia is a distinct subtype or not.
Comorbidity with obsessive-compulsive symptoms is
often misdiagnosed or even neglected by psychiatrists.
6. DSM-IV criteria for schizophrenia describe some
schizophrenic individuals as manifesting symptoms of
both obsessive-compulsive disorder and schizophrenia.
The biological basis of obsessive-compulsive disorder
has been extensively studied, including neurological
disorders, brain injury, as well as genetic,
neuropsychological, and neuroimaging studies.
Epidemiologic reviews of schizophrenia revealed that
the probability for comobidity with obsessive
compulsive disorder is 3.5% to 15%.
Management of Obsessive-CompulsiveManagement of Obsessive-Compulsive
Schizophrenia (cont’d)Schizophrenia (cont’d)
7. Obsessive-compulsive comorbidity leads to a poorer
clinical course, lower levels of functioning, and longer
periods of hospitalization compared with
schizophrenics who are not obsessive-compulsive.
Although no standard treatment has been established
for treatment of obsessive-compulsive schizophrenia, a
series of case reports indicated that clozapine improved
the obsessive-compulsive symptom.
Management of Obsessive-CompulsiveManagement of Obsessive-Compulsive
Schizophrenia (cont’d)Schizophrenia (cont’d)
8. A combination of risperidone (mean dose, 2.75
mg/day) and a selective serotonin reuptake inhibitor
improve refractory obsessive-compulsive
schizophrenia.
Well-designed double-blind studies are required to
assess the effectiveness of atypical neuroleptics on
obsessive-compulsive symptoms.
Management of Obsessive-CompulsiveManagement of Obsessive-Compulsive
Schizophrenia (cont’d)Schizophrenia (cont’d)
9. Schizophrenia with DepressionSchizophrenia with Depression
Median prevalence of depression is about 25% in
schizophrenia.
Depressive comorbidity is associated with substantial
suffering, decrease in functional status, poor outcome,
and suicide idea/behavior.
Differential diagnoses for schizophrenics with
depression including organic/medical condition,
affective/hedonic dysregulation, adverse effect of
medication, and substance abuse.
10. Schizophrenia with Depression (cont’d)Schizophrenia with Depression (cont’d)
Negative symptoms may present as a phenotype of
depression in schizophrenia.
Neuroleptics can induce akinesia and akathisia, which
mimics depression in schizophrenia.
Neuroleptics might directly induce dysphoria
associated with depressive symptoms.
11. Lithium has reported to be the most effective
pharmacologic intervention among various treatment
strategies.
Psychosocial intervention is also effective to reduce
depressive symptoms.
Imipramine significantly improves Clinical Global
Impression Scale scores as well as depressive
symptoms.
Schizophrenia with Depression (cont’d)Schizophrenia with Depression (cont’d)
12. Psychotic symptoms did not change over time during
the use of imipramine.
These findings suggest that an adjunctive
antidepressant may help to improve depression with
schizophrenia.
A long-term double-blind trial has also revealed that
imipramine reduced the relapse rate for
schizophrenia.
Schizophrenia with Depression (cont’d)Schizophrenia with Depression (cont’d)
13. The suicide attempt rate in schizophrenia has been
estimated to be 25-50%, lifetime.
The completed suicide rate in the US general
population is estimated as 11.4 per 100,000.
The rate of completed suicide among patients with
schizophrenia is usually reported to be between 9-
13%, 25 times greater than in the general population25 times greater than in the general population..
The estimated annual number of suicides in the US
for schizophrenia is 3200-4000, 12% of total suicides.
Schizophrenia with SuicideSchizophrenia with Suicide
14. Suicide accounted for 52% and 35% of deaths
amongst first-episode male and female
schizophrenic patients, respectively.
Suicide risk was particularly increased during the
first year of follow-up.
Schizophrenia with Suicide (cont’d)Schizophrenia with Suicide (cont’d)
15. 1)Previous suicide attempts
2) Depression
3) Hopelessness
4) Substance abuse
5) Male sex
6)Insight, i.e. awareness of the effects of the illness on social
and cognitive function and fear of worsening condition.
7)Recent discharge from hospital without adequate treatment
planning
8) Caucasian race
9)Deteriorating health with high levels of premorbid
functioning
10) Adverse life events
Risk Factors for Suicide inRisk Factors for Suicide in
SchizophreniaSchizophrenia
16. Reducing the risk of suicidality in schizophrenia
requires, in the first instance, improving overall
outcome.
Controlling psychosis, depression, limiting substance
abuse, preventing or reversing cognitive
deterioriation, improving general health, facilitiating
work and social function, and decreasing isolation
from family and others are necessary to achieve a
meaningful reduction in the suicide rate.
Schizophrenia with Suicide (cont’d)Schizophrenia with Suicide (cont’d)
17. Atypical antipsychotic drugs, utilized early in the
course of illness, coupledcoupled with intensive
psychosocial support in an outpatient setting,
appear to be the best means to achieve these
ambitious goals.
Schizophrenia with Suicide (cont’d)Schizophrenia with Suicide (cont’d)
18. Schizophrenia and ComorbidSchizophrenia and Comorbid
Substance AbuseSubstance Abuse
35% of schizophrenics are currently diagnosed with
alcoholic abuse. Other abused substances were cocaine
(20%), heroin (3%), and marijuana (15%).
Nicotine use was the most common, with a range of
70% to 90% in patients with schizophrenia.
Heavy smokers (more than 20 cigarettes per day) had 4
times the risk for multiple substance abuse.
High nicotine levels also increase P450 enzyme
activity, resulting in the necessity of higher dose
neuroleptics for effective treatment.
19. Screening and assessment for substance abuse are
important for an early intervention.
Strategy for early screening has been useful in
evaluating risk for substance abuse.
Substance abuse is associated with relapse of
psychosis, multiple hospitalization, legal
problems/violence, social isolation/homelessness,
noncompliant with medication, HIV risk, and family
problems.
Schizophrenia and ComorbidSchizophrenia and Comorbid
Substance AbuseSubstance Abuse (cont’d)(cont’d)
20. Specific psychosocial approaches, including behavioral
therapy, are effective for the treatment of stimulant
abusers.
However, many limitations are considered in
schizophrenia when planning treatment strategy,
including therapeutic alliance, low motivation,
cognitive limitations, low self-efficacy, and
maladaptive interpersonal skills.
Schizophrenia and ComorbidSchizophrenia and Comorbid
Substance AbuseSubstance Abuse (cont’d)(cont’d)
21. A study showed that low motivation was found in
abusers of alcohol (53%), cocaine (66%), marijuana
(71%), heroin (87%), and nicotine (91%) in 224 patients
with schizophrenia.
Medication strategies have been reviewed for nicotine
abuse with schizophrenia.
Several studies reported that there was a significant
decrease in reported daily cigarette use during atypical
neuroleptics (clozapine) compared with the level of use
when patients had been treated with typical neuroleptics.
Schizophrenia and ComorbidSchizophrenia and Comorbid
Substance AbuseSubstance Abuse (cont’d)(cont’d)
22. Schizophrenia and Persistent AggressiveSchizophrenia and Persistent Aggressive
BehaviorBehavior
Violence is the major cause for admission to acute
psychiatry units and hospitals.
Epidemiology revealed that co-occurring substance
abuse and intoxication increase the risk of violence in
patients with schizophrenia.
One study of 20,000 samples revealed that
schizophrenics had 5- to 6-fold higher probability for
violence.
23. High risk of violence in schizophrenia has been a
robust finding in nearly every culture in the world.
Ten percent of patients attack others within 24 hours
after their admission in hospitals.
Short-term and long-term studies show the same
incidence, with 5% to 7% probability for incidence of a
violent attack.
Schizophrenia and Persistent AggressiveSchizophrenia and Persistent Aggressive
Behavior (cont’d)Behavior (cont’d)
24. Assessment of the cause of the violent episode was
particularly important, including the need to rule out somatic
conditions (acute or chronic), adverse effect of medications,
comorbidity with substance abuse, and risk assessment by
criminal record.
The pattern of violence was divided into transient and
persistent.
Transient violence is associated with environmental factors
and positive symptoms of psychosis, while persistent violence
is related to neurologic impairment and psychopathy, but not
aggressiveness or positive symptoms.
Schizophrenia and Persistent AggressiveSchizophrenia and Persistent Aggressive
Behavior (cont’d)Behavior (cont’d)
25. Several medication strategies are considered for
treatment of persistently aggressive psychotic patients,
including conventional neuroleptics, atypical
neuroleptics, and mood stabilizers.
Valproate has been well used to treat violent behavior.
Lithium and b-blocker also have been effective to
reduce violence on some schizophrenics.
Schizophrenia and Persistent AggressiveSchizophrenia and Persistent Aggressive
Behavior (cont’d)Behavior (cont’d)
26. Cognitive-Functional Rehabilitation inCognitive-Functional Rehabilitation in
Older PatientsOlder Patients
Cognitive impairment without dementia was
common in patients with old schizophrenics
patients and independent of manifestations of
negative symptoms.
Cognitive deficits in schizophrenia may result
from physical comorbidity, medication (eg,
anticholinergics), substance abuse, sensory
deficits, depression, and institutionlization.
27. Psychosocial intervention in addition to
pharmacotherapy has been effective in chronic
schizophrenics with cognitive impairment.
Theses interventions include cognitive behavioral
therapy (CBT), cognitive rehabilitation, and social skill
training (SST).
Cognitive-Functional Rehabilitation inCognitive-Functional Rehabilitation in
Older Patients (cont’d)Older Patients (cont’d)
28. Negative symptoms as well as positive symptoms were
improved for both a schizophrenic group with CBT.
For older schizophrenics, combination of CBT and SST
(Cognitive Behavioral Social Skill Training
[CCBSST]) was found to be useful to improve their
cognitive skills.
Cognitive-Functional Rehabilitation inCognitive-Functional Rehabilitation in
Older Patients (cont’d)Older Patients (cont’d)
29. Late-onset schizophrenia is that which presents inLate-onset schizophrenia is that which presents in
patients over 45 years of age.patients over 45 years of age.
Originally thought to be rare, it is generallyOriginally thought to be rare, it is generally
recognised that a significant number of patients withrecognised that a significant number of patients with
a diagnosis of schizophrenia had their first psychotica diagnosis of schizophrenia had their first psychotic
episode later in life.episode later in life.
Treatment of schizophrenia in older patients presentsTreatment of schizophrenia in older patients presents
a therapeutic challenge for clinicians.a therapeutic challenge for clinicians.
Late Onset Schizophrenia (cont’d)Late Onset Schizophrenia (cont’d)
30. Late Onset Schizophrenia (cont’d)Late Onset Schizophrenia (cont’d)
These patients are likely to have comorbid illnessesThese patients are likely to have comorbid illnesses
and to be taking multiple medications.and to be taking multiple medications.
Furthermore, age-related pharmacokinetic changesFurthermore, age-related pharmacokinetic changes
place older patients at increased risk for drugplace older patients at increased risk for drug
interactions and adverse effects of antipsychotics.interactions and adverse effects of antipsychotics.
Low doses of the newer (atypical) antipsychoticsLow doses of the newer (atypical) antipsychotics
((risperidone, or olanzapinerisperidone, or olanzapine )) are preferred in theare preferred in the
treatment of late-onset schizophrenia owing to theirtreatment of late-onset schizophrenia owing to their
low propensity to cause extrapyramidal side effects.low propensity to cause extrapyramidal side effects.
31. Treating First EpisodesTreating First Episodes
Young patients with a first episode of psychosis respondYoung patients with a first episode of psychosis respond
equally well to first- and second-generation drugs, butequally well to first- and second-generation drugs, but
tolerability of the drug regime is especially important intolerability of the drug regime is especially important in
this population.this population.
Good choices are medications such as low-dose first-Good choices are medications such as low-dose first-
generation drugs, orgeneration drugs, or risperidone, or olanzapinerisperidone, or olanzapine where thewhere the
starting dose can also be the therapeutic dosestarting dose can also be the therapeutic dose (where slow-(where slow-
dose increase is not required because blood pressure remainsdose increase is not required because blood pressure remains
stable).stable).
32. Since, these drugs will be required indefinitely long-Since, these drugs will be required indefinitely long-
term side effects need to be anticipated,term side effects need to be anticipated, tardivetardive
dyskinesia on one hand, sexual problems, weight gaindyskinesia on one hand, sexual problems, weight gain
and diabetes on the other.and diabetes on the other.
Low-dose, extended dosingLow-dose, extended dosing (every second or third(every second or third
day) regimens ofday) regimens of first-generation drugsfirst-generation drugs may be wellmay be well
suited for many patients with first episodes.suited for many patients with first episodes.
Treating First Episodes (cont’dTreating First Episodes (cont’d))
33. Patients known to bePatients known to be nonadherentnonadherent to regularto regular
medication will do better on those drugs that aremedication will do better on those drugs that are
relativelyrelatively tightly bound to the D2 receptortightly bound to the D2 receptor (where(where
relapse due to a brief period of noncompliance is arelapse due to a brief period of noncompliance is a
lesser risk).lesser risk).
Monthly depot medicationMonthly depot medication isis stillstill thethe treatment oftreatment of
choicechoice for the extremely nonadherent.for the extremely nonadherent.
Treating Nonadherent PatientsTreating Nonadherent Patients
34. Second-generation antipsychoticSecond-generation antipsychotic drugs have adrugs have a largerlarger
window of safetywindow of safety between therapeutic effects andbetween therapeutic effects and
EPS than do the older drugs.EPS than do the older drugs.
In other wordsIn other words,, the 80% level of D2 occupancy is notthe 80% level of D2 occupancy is not
reached with standard therapeutic doses.reached with standard therapeutic doses.
Treating Patients Who HaveTreating Patients Who Have
EPSEPS
35. For patients with persistent, severe tardive dyskinesia,For patients with persistent, severe tardive dyskinesia,
clozapineclozapine has been found to behas been found to be the best choicethe best choice..
Development ofDevelopment of partial agonistspartial agonists such assuch as aripiprazolearipiprazole,,
with high affinity blockingwith high affinity blocking ((permitting 10%permitting 10% ofof
endogenous dopamine to cross over to the postsynaptic cell).endogenous dopamine to cross over to the postsynaptic cell).
The high occupancy of serotonin-2A receptors byThe high occupancy of serotonin-2A receptors by
olanzapine and risperidoneolanzapine and risperidone did not alterdid not alter the D2the D2
occupancyoccupancy (required for(required for the antipsychotic thresholdthe antipsychotic threshold or theor the
D2 occupancy forD2 occupancy for the threshold for EPS)the threshold for EPS)..
Treating Patients Who Have EPSTreating Patients Who Have EPS
(cont’d(cont’d((
36. On the other hand, prolactin-sparing drugsOn the other hand, prolactin-sparing drugs
(principally clozapine, quetiapine and, to a(principally clozapine, quetiapine and, to a
lesser extent, olanzapine) have not yet beenlesser extent, olanzapine) have not yet been
shown to be safe in pregnancy.shown to be safe in pregnancy.
Clozapine is unwise during pregnancy becauseClozapine is unwise during pregnancy because
of the theoretical possibility of seizureof the theoretical possibility of seizure
induction and agranulocytosis in the fetus.induction and agranulocytosis in the fetus.
Treating WomenTreating Women
37. Because of rising estrogen levels at this time andBecause of rising estrogen levels at this time and
estrogen modulation of the dopamine receptor, thereestrogen modulation of the dopamine receptor, there
is relative protection against psychotic relapse .is relative protection against psychotic relapse .
A drug-free first trimester is ideal but not alwaysA drug-free first trimester is ideal but not always
achievable.achievable.
If antipsychotics are necessary,If antipsychotics are necessary, low-dose haloperidollow-dose haloperidol
has the best safety record throughout pregnancy, withhas the best safety record throughout pregnancy, with
dose reduction prior to the anticipated day of birthdose reduction prior to the anticipated day of birth (to(to
facilitate labor and minimize drug withdrawal effects in the neonate).facilitate labor and minimize drug withdrawal effects in the neonate).
Treating Women (contTreating Women (cont.(.(
38. Patients with a family history of osteoporosis are bestPatients with a family history of osteoporosis are best
notnot treated with drugs thattreated with drugs that raise prolactin levels.raise prolactin levels.
This is especially true for women because theyThis is especially true for women because they
develop osteoporosis at a younger age than men.develop osteoporosis at a younger age than men.
Normal serum prolactin levels are considered to beNormal serum prolactin levels are considered to be
between 5 and 25 micrograms/L.between 5 and 25 micrograms/L.
Treating Patients With a Family History ofTreating Patients With a Family History of
OsteoporosisOsteoporosis
39. The QTc interval (approximate range is 350-The QTc interval (approximate range is 350-
440 milliseconds [ms]) represents the duration440 milliseconds [ms]) represents the duration
of ventricular depolarization andof ventricular depolarization and
repolarization.repolarization.
It is generally accepted that QTc intervalsIt is generally accepted that QTc intervals
exceeding 500 ms are associated with anexceeding 500 ms are associated with an
increased risk of a lethal paroxysmalincreased risk of a lethal paroxysmal
ventricular tachycardiaventricular tachycardia (torsades de pointes).(torsades de pointes).
Treating Cardiac Patients or Those With aTreating Cardiac Patients or Those With a
Family History of Cardiac DiseaseFamily History of Cardiac Disease
40. Thioridazine prolonged the mean QTc interval byThioridazine prolonged the mean QTc interval by
about 35.6 ms and ziprasidone by 20.3 ms, comparedabout 35.6 ms and ziprasidone by 20.3 ms, compared
with haloperidol (4.7 ms).with haloperidol (4.7 ms).
Quetiapine, olanzapine, and risperidone prolong theQuetiapine, olanzapine, and risperidone prolong the
QT interval less so than haloperidol.QT interval less so than haloperidol.
Treating Cardiac Patients or Those With aTreating Cardiac Patients or Those With a
Family History of Cardiac Disease (cont’dFamily History of Cardiac Disease (cont’d((
41. The novel antipsychotics have more propensity forThe novel antipsychotics have more propensity for
inducing insulin resistance:inducing insulin resistance: clozapine, olanzapine,clozapine, olanzapine,
andand quetiapinequetiapine cause the highest rates of diabetes;cause the highest rates of diabetes;
risperidonerisperidone andand ziprasidoneziprasidone are associated with lowerare associated with lower
rates.rates.
Patients with a family history of diabetes and withPatients with a family history of diabetes and with
other concurrent risk factors should beother concurrent risk factors should be treated withtreated with
first-generation antipsychotics or with risperidone orfirst-generation antipsychotics or with risperidone or
ziprasidone.ziprasidone.
Treating Patients With a Family History ofTreating Patients With a Family History of
DiabetesDiabetes
42. SummarySummary
Adequate assessment and treatment are important to
improve prognosis of schizophrenic patients.
Systematic assessment and efficient medication are
essential for management of comrobidity of
schizophrenia.
In addition, psychosocial treatment has been proved to
be effective on several comorbid conditions.
However, multiple comorbidities are also common and
lead patients to be more refractory in schizophrenia.
Further, studies are required to develop more
effective treatment on comorbidities in
schizophrenia.
