hanipsych, comorbidity in schizophrenia

Prof. Hani Hamed Dessoki

Prof. of Psychiatry

Beni Suef University

2015

IntroductionIntroduction

Psychiatric comorbidities are common Psychiatric comorbidities are common among patients with schizophreniaamong patients with schizophrenia. . Substance abuse comorbidity Substance abuse comorbidity predominatespredominates. .

Anxiety and depressive symptoms are also Anxiety and depressive symptoms are also very common throughout the course of very common throughout the course of illness, with an estimated prevalence of illness, with an estimated prevalence of 15% for panic disorder15% for panic disorder, , 29% for 29% for posttraumatic stress disorderposttraumatic stress disorder, and , and 23% 23% for obsessivefor obsessive--compulsive disordercompulsive disorder..


It is estimated that comorbid It is estimated that comorbid depression occurs in 50% of depression occurs in 50% of patients, and perhaps patients, and perhaps (conservatively) 47% of patients also (conservatively) 47% of patients also have a lifetime diagnosis of comorbid have a lifetime diagnosis of comorbid substance abuse. substance abuse.


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.

Management of Obsessive-Compulsive Management 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.

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-Compulsive Management of Obsessive-Compulsive Schizophrenia (cont’d)Schizophrenia (cont’d)

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.


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.


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.

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.

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.


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.


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

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)

1)Previous suicide attempts2) Depression3) Hopelessness4) Substance abuse5) Male sex6)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 in Risk Factors for Suicide in SchizophreniaSchizophrenia

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.


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 and Comorbid Schizophrenia 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.

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 Comorbid Schizophrenia and Comorbid Substance AbuseSubstance Abuse (cont’d) (cont’d)

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.


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 Persistent Aggressive Schizophrenia 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.

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 Aggressive Schizophrenia and Persistent Aggressive Behavior (cont’d)Behavior (cont’d)

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.


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.


Cognitive-Functional Rehabilitation in Cognitive-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.

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 in Cognitive-Functional Rehabilitation in Older Patients (cont’d)Older Patients (cont’d)

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 in Cognitive-Functional Rehabilitation in Older Patients (cont’d)Older Patients (cont’d)

Late-onset schizophrenia is that which presents in Late-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 generally Originally thought to be rare, it is generally recognised that a significant number of patients with recognised that a significant number of patients with a diagnosis of schizophrenia had their first psychotic a diagnosis of schizophrenia had their first psychotic episode later in life. episode later in life.

Treatment of schizophrenia in older patients presents Treatment 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)

Late Onset Schizophrenia (cont’d)Late Onset Schizophrenia (cont’d)

These patients are likely to have comorbid illnesses These patients are likely to have comorbid illnesses and to be taking multiple medications. and to be taking multiple medications.

Furthermore, age-related pharmacokinetic changes Furthermore, age-related pharmacokinetic changes place older patients at increased risk for drug place 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) antipsychotics Low doses of the newer (atypical) antipsychotics ((risperidone, or olanzapinerisperidone, or olanzapine )) are preferred in the are preferred in the treatment of late-onset schizophrenia owing to their treatment of late-onset schizophrenia owing to their low propensity to cause extrapyramidal side effects. low propensity to cause extrapyramidal side effects.

Treating First EpisodesTreating First Episodes

Young patients with a first episode of psychosis respond Young patients with a first episode of psychosis respond equally well to first- and second-generation drugs, but equally well to first- and second-generation drugs, but tolerability of the drug regime is especially important in tolerability 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, or generation drugs, or risperidone, or olanzapinerisperidone, or olanzapine where the where the starting dose can also be the therapeutic dose starting dose can also be the therapeutic dose (where slow-(where slow-dose increase is not required because blood pressure remains dose increase is not required because blood pressure remains stable).stable).

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, tardive tardive dyskinesia on one hand, sexual problems, weight gain dyskinesia 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 of day) regimens of first-generation drugsfirst-generation drugs may be well may 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))

Patients known to be Patients known to be nonadherentnonadherent to regular to regular medication will do better on those drugs that are medication will do better on those drugs that are relatively relatively tightly bound to the D2 receptortightly bound to the D2 receptor (where (where relapse due to a brief period of noncompliance is a relapse due to a brief period of noncompliance is a lesser risk). lesser risk).

Monthly depot medicationMonthly depot medication is is stillstill the the treatment of treatment of choicechoice for the extremely nonadherent. for the extremely nonadherent.

Treating Nonadherent PatientsTreating Nonadherent Patients

Second-generation antipsychoticSecond-generation antipsychotic drugs have a drugs have a larger larger window of safetywindow of safety between therapeutic effects and between 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 not the 80% level of D2 occupancy is not reached with standard therapeutic doses.reached with standard therapeutic doses.

Treating Patients Who Have Treating Patients Who Have EPS EPS

For patients with persistent, severe tardive dyskinesia, For patients with persistent, severe tardive dyskinesia, clozapineclozapine has been found to be has been found to be the best choicethe best choice..

Development of Development of partial agonistspartial agonists such as such as aripiprazolearipiprazole, , with high affinity blocking with high affinity blocking ((permitting 10%permitting 10% of of 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 by The high occupancy of serotonin-2A receptors by olanzapine and risperidoneolanzapine and risperidone did not alterdid not alter the D2 the D2 occupancy occupancy (required for (required for the antipsychotic thresholdthe antipsychotic threshold or the or the D2 occupancy for D2 occupancy for the threshold for EPS)the threshold for EPS). .

Treating Patients Who Have EPS Treating Patients Who Have EPS (cont’d(cont’d((

On the other hand, prolactin-sparing drugs On the other hand, prolactin-sparing drugs (principally clozapine, quetiapine and, to a (principally clozapine, quetiapine and, to a lesser extent, olanzapine) have not yet been lesser extent, olanzapine) have not yet been shown to be safe in pregnancy. shown to be safe in pregnancy.

Clozapine is unwise during pregnancy because Clozapine is unwise during pregnancy because of the theoretical possibility of seizure of the theoretical possibility of seizure induction and agranulocytosis in the fetus.induction and agranulocytosis in the fetus.

Treating WomenTreating Women

Because of rising estrogen levels at this time and Because of rising estrogen levels at this time and estrogen modulation of the dopamine receptor, there estrogen 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 always A 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, with has the best safety record throughout pregnancy, with dose reduction prior to the anticipated day of birth dose 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.(.(

Patients with a family history of osteoporosis are best Patients with a family history of osteoporosis are best notnot treated with drugs that treated with drugs that raise prolactin levels.raise prolactin levels.

This is especially true for women because they This 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 be Normal 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 of Treating Patients With a Family History of OsteoporosisOsteoporosis

The QTc interval (approximate range is 350-The QTc interval (approximate range is 350-440 milliseconds [ms]) represents the duration 440 milliseconds [ms]) represents the duration of ventricular depolarization and of ventricular depolarization and repolarization.repolarization.

It is generally accepted that QTc intervals It is generally accepted that QTc intervals exceeding 500 ms are associated with an exceeding 500 ms are associated with an increased risk of a lethal paroxysmal increased risk of a lethal paroxysmal ventricular tachycardia ventricular tachycardia (torsades de pointes).(torsades de pointes).

Treating Cardiac Patients or Those With a Treating Cardiac Patients or Those With a Family History of Cardiac DiseaseFamily History of Cardiac Disease

Thioridazine prolonged the mean QTc interval by Thioridazine prolonged the mean QTc interval by about 35.6 ms and ziprasidone by 20.3 ms, compared about 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 the Quetiapine, olanzapine, and risperidone prolong the QT interval less so than haloperidol.QT interval less so than haloperidol.

Treating Cardiac Patients or Those With a Treating Cardiac Patients or Those With a Family History of Cardiac Disease (cont’dFamily History of Cardiac Disease (cont’d((

The novel antipsychotics have more propensity for The novel antipsychotics have more propensity for inducing insulin resistance: inducing insulin resistance: clozapine, olanzapine,clozapine, olanzapine, andand quetiapine quetiapine cause the highest rates of diabetes; cause the highest rates of diabetes; risperidonerisperidone and and ziprasidoneziprasidone are associated with lower are associated with lower rates.rates.

Patients with a family history of diabetes and with Patients with a family history of diabetes and with other concurrent risk factors should be other concurrent risk factors should be treated with treated with first-generation antipsychotics or with risperidone or first-generation antipsychotics or with risperidone or ziprasidone.ziprasidone.

Treating Patients With a Family History of Treating Patients With a Family History of DiabetesDiabetes

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.

Hanipsych, comorbidity in schizophreniaHanipsych, comorbidity in schizophrenia

hanipsych, comorbidity in schizophrenia

Documents

chronic schizophrenia

obsessivecompulsive

comorbid depression

substance abuse comorbidity

depressive symptoms

phenotype of depression

manifesting symptoms

depressionnegative symptoms