Consider Patient Preference when Prescribing Antipsychotics for Schizophrenia

Patient preference, tolerance and efficacy should be considered to achieve optimal therapeutic results.

Pharmacologic Management of the Schizophrenic Patient
Pharmacologic Management of the Schizophrenic Patient

Schizophrenia is a chronic and disabling mental illness that has affected millions of people all over the world.1 Individuals with schizophrenia may experience difficulties relating to the people in their environment as a result of a breakdown in thought processes and deficit in providing normal emotional responses to others.3

Schizophrenia is defined as a psychotic thought disorder characterized by a mixture of symptoms that may involve alterations in perception, cognition, emotions, behavior, attention, concentration, motivation, and judgment.1,2

About 60% to 70% of patients with schizophrenia are not adequately treated for their symptoms.19 Because patients require long-term antipsychotic maintenance treatment, the effectiveness of antipsychotic medications is vital to ensure they can perform activities of daily living and sustain an adequate quality of life.21

Etiology & clinical characteristics

The development of schizophrenia is not based on a single inherited predisposition, but on multiple physical, mental, inherited, and acquired dispositions that can lead to the disorder.

Although the etiology of schizophrenia still remains unclear, it is certain that unfavorable hereditary predispositions combined with unfavorable life experience play a role.8

The clinical characteristics of schizophrenia may include hallucinations, delusions, loosening of associations, misinterpretation of reality, and catatonia.2

The most commonly identified positive symptoms of schizophrenia are hallucinations and delusions, with auditory hallucinations being the most commonly identified in 74% of schizophrenics.3

Negative symptoms include absences of normal capabilities such as emotional withdrawal, blunted affect avolition, anhedonia, or alogia, which are fundamental to understanding the functional limitations of the disorder.4-6 The presence of these symptoms must be significant enough to demonstrate decline in social and/or occupational functioning.7

The combination of enduring negative symptoms and episodic displays of positive symptoms of schizophrenia can have a profound impact on activities of daily living such as social functionality and quality of life.9 

Diagnosis & Subtypes

The diagnosis of schizophrenia is based on the presence of two or more symptoms  for a significant portion of time during a one-month period, according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-V).10

After disease onset, there must be a significant portion of time where major areas of functioning are impaired. Signs of the disturbance last for at least six months and include at least one month of symptoms.11,12 During prodromal or residual periods, the signs of the disturbance may be manifested by only negative symptoms or two or fewer symptoms.11

In order for a patient to receive a diagnosis of schizophrenia, other disorders such as schizoaffective and mood disorders with psychotic features must be ruled out.12 Symptoms of major depressive episode, manic episodes, or mixed episode occurring during the active phase of symptoms are not indicative of schizophrenia. Disturbances are not the result of a direct physiological effect of a substance.13,14

When a diagnosis of schizophrenia is made, a patient can be categorized as one of four main subtypes -- paranoid, disorganized, undifferentiated, or catatonic.15

Paranoid schizophrenia is defined as the preoccupation with one or more delusions or frequent auditory hallucinations. Disorganized schizophrenia consists of disorganize speech and behavior, and flat or inappropriate affect.15,16

In catatonic schizophrenia, a patient's prominent motor symptoms have no reactivity to the environment. In undifferentiated schizophrenia symptoms are present, but do not meet criteria for paranoid, disorganized, or catatonic type.17

Pharmacotherapy

The pharmacotherapy of schizophrenia is generally synonymous with the use of antipsychotic medications. Since the synthesis of the first antipsychotic medication chlorpromazine in the 1950s, the current market is filled with antipsychotic medication options.18

Chlorpromazine served as the prototype for many other antipsychotics and led to the creation of additional first generation antipsychotics, also called typical antipsychotics (Tables 1, 2).

Table 1: Typical Antipsychotic Medications (First Generation Antipsychotics)

 
Dosage forms
Average dose titrated to (mg) Relative potency D2 Effects 5HT2 Effects Muscarinic effects Alpha-1 adrenergic effects Antihistamine effects
Chlorpromazine(Thorazine)
T, I
600-800 100 ++++ ++++ ++++ ++++ ++++
Fluphenazine (Prolixin)
T, L, I, I (LA)
10-20 2 ++++ ++ + + ++
Perphenazine (Trilafon)
T
60-80 10 ++++ ++++ + ++ +++
Trifluoperazine (Stelazine)
T
30-40 5 ++++ +++ + ++ ++
Thioridazine (Mellaril)
T
600-800 100 ++++ ++++ ++++ ++++ ++++
Mesoridazine (Serentil) + withdrawn from US market in 2004
T
300-400 50 ++++ ++++ +++ ++++ ++++
Haloperidol (Haldol)
T, L, I, I (LA)
10-20 2 ++++ ++ + + +
Molindone (Moban) *discontinued by manufacturer in 2010
T
50-100 10 +++ + ++ + +
Thiothixene (Navane)
C
30-40 5 ++++ + + ++ +++
Loxapine (Loxitane)
C
75-100 12.5 +++ ++++ ++ +++ ++++
Source: Albers LJ, Hahn RK, Reist C. (2008). Handbook of Psychiatric Drugs. Blue Jay, CA: Current Clinical Strategies Pub.

Level/degree of effect
(+) = low
(++) = moderate
(+++) = high
(++++) = very high



Table 2: Atypical Antipsychotic Medications (Second Generation Antipsychotics)

Generic (brand)
Dosage forms
Average dose (mg) Chlorpromazine equivalents (mg) *D1 Effects *5HT2 Effects *Muscarinic effects (M1) *Alpha-1 adrenergic effects *Antihistamine effects (H1)
Clozapine (Clozaril,FazaClo)
T,ODT
300 - 600 60 126 16 1.9 160 6
Aripiprazole (Abilify)
T,ODT,L,I
15 - 30 2 - 4 265 3.4 >10,000 57 61
Risperidone (Risperdal)
T,ODT,L, I(LA)
2 - 8 1 - 2 430 0.5 >10,000 2 20
Olanzapine (Zyprexa)
T,ODT,I
5 - 20 3 31 4 1.9 19 7
Quetiapine (Seroquel)
T,T(ER)
400 - 600 50 455 295 120 7 11
Ziprasidone (Geodon)
C,I
80 - 160 5 - 10 525 0.4 >1000 11 50
Paliperidone (Invega)
T(ER), I(LA)
6 -12 2 - 1.2 1.2 10 3.4
Asenapine (Saphris)
T(sublingual)
5 - 10 N/A 1.4 0.06 8128 1.2 6.2
Iloperidone (Fanapt)
T
12 - 24 N/A 216 5.6 >1000 - 473
Lurasidone (Latuda)
T
40 - 160 N/A N/A N/A N/A N/A N/A
*Receptor Affinity Binding (Ki data)
Source: Albers LJ, Hahn RK, Reist C. (2011). Handbook of Psychiatric Drugs. Blue Jay, CA: Current Clinical Strategies Pub.

The first atypical antipsychotic clozapine was also discovered in the 1950s, but was not introduced onto the market until the 1970s. Clozapine became recognized for its use in a subset of individuals with psychotic disorder who did not benefit from conventional antipsychotic medications.19,20 There are now numerous atypical antipsychotic medications available (Tables 3, 4).

Both typical and atypical antipsychotic medications have been shown to assist in treating positive symptoms (e.g., hallucination and delusion), negative symptoms (e.g., social withdrawal and poverty of speech), and cognitive symptoms (e.g., reduction in working memory and attention) associated with schizophrenia.19

Table 3: Typical Antipsychotic Medications Adverse Effects

Typical antipsychotics
Sedating effects
Anticholinergic effects Extrapyramidal side effects Hypotensive effects
Chlorpromazine
High
High Low IM-High PO-Moderate
Fluphenazine
Low
Low Very high Low
Haloperidol
Very low
Very low Very high Very low
Loxapine
Moderate
Low Moderate Moderate
Molindone
Very low
Low Moderate Low
Perphenazine
Low
Low High Low
Pimozide
Low
Low High Very low
Thioridazine
High
High Low High
Thiothixene
Low
Low High Low
Trifluoperazine
Low
Low High Low
Source: College of Psychiatric and Neurologic Pharmacists. 2010-2011 BCPP examination review and recertification course. Orth-McNeil Jansseen Scientific Affairs, LLC. 2010.


Table 4: Atypical Antipsychotic Medications Adverse Effects

Dose-related extrapyramidal side effects
Risperidone=paliperidone>olanzapine=ziprasidone=aripiprazole=iloperidone>quetiapine=clozapine
Sedation
Clozapine>quetiapine>paliperidone=clozapine=risperidone=ziprasidone=aripiprazole=iloperidomne=asenapine
Anticholinergic
Clozapine>olanzapine>quetiapine>paliperidone=risperidone=ziprasidone=aripiprazole=iloperidone=asenapine
Weight gain
Clozapine=olanzapine>quetiapine=risperidone=paliperidone>iloperidone>aspenapine>ziprasidone>aripiprazole
Lipid abnormalities
Clozapine=olanzapine>quetiapine>iloperidone>asenapine>risperidone>paliperidone>ziprasidone>aripiprazole
Lowering of seizure threshold (dose-related)
Clozapine>olanzapine=risperidone=paliperidone=quetiapine, Ziprasidone=aripiprazole=iloperidone=asenapine
Glucose intolerance
Clozapine=olanzapine>quetiapine=risperidone=paliperidone>Ziprasidone=aripiprazole-iloperidone=asenapine
Increased prolactin level
Paliperidone>risperidone>olanzapine=Ziprasidone=quetiapine=clozapine=iloperidone=asenapine>aripiprazole
Source: College of Psychiatric and Neurologic Pharmacists. 2010-2011 BCPP examination review and recertification course. Orth-McNeil Jansseen Scientific Affairs, LLC. 2010.

Clinicians must be cognizant of the available typical and atypical antipsychotics, dosage range, relative potency, and side effect profiles.21,22

The selection of the appropriate antipsychotic medication is at the discretion of the prescribing provider but patient preference, tolerance, and efficacy should also be considered to increase the probability of achieving optimal therapeutic results.22

Abimbola Farinde, PharmD, MS, is a clinical staff pharmacist at Parkland Hospital in Dallas, Texas.

References

  1. Gupta S, Kulhara P. What is schizophrenia: A neurodevelopmental or neurodegenerative disorder or a combination of both? A critical analysis. Indian J Psychiatry. 2010; 52: 21-27. 
  2. Hahn RK, Albers LJ, Reist C. Psychiatry. Blue Jay, California: Current Clinical Strategies Publishing; 2008. 
  3. Kandil F, Pedersen A, Wehnes J et al. High-level, but not low-level, motion perception is impaired in patients with schizophrenia. Neuropsychology. 2013; 27: 60-68. 
  4. Rollins A, Bond G, Lysaker P et al. Coping with positive and negative symptoms of schizophrenia. Am J Psychiatr Rehabil. 2010; 13: 208-223. 
  5. Kirkpatrick B, Fenton WS, Carpenter WT et al. The NIMH-MATRICS consensus statement on negative symptoms. Schizophr Bull. 2006; 32: 214-219. 
  6. Flanagan E, Solomon L, Johnson A et al. Considering DSM-5: The personal experience of schizophrenia in relation to the DSM-IV-TR criteria. Psychiatry. 2012;75:375-86.
  7. Schaub D, Brüne M, Jaspen E et al. The illness and everyday living: Close interplay of psychopathological syndromes and psychosocial functioning in chronic schizophrenia. Eur Arch Psychiatry Clin Neurosci. 2011; 261: 85-93. 
  8. Strauss J, Bowers M, Keith S et al. What is schizophrenia? Schizophr Bull. 1984; 10: 8-10. 
  9. Hoffmann H, Kupper Z, Kunz B. Hopelessness and its impact on rehabilitation outcome in schizophrenia — An exploratory study. Schizophr Res. 2000; 43: 147-58. 
  10. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA: American Psychiatric Publishing. 
  11. Keller W, Fischer B, Carpenter J. Revisiting the diagnosis of schizophrenia: Where have we been and where are we going? CNS Neurosci Ther. 2011; 17: 83-88. 
  12. Idrees M, Khan I, Irfan M et al. First rank of symptoms in the diagnosis of schizophrenia. J Postgrad Med Inst. 2010; 24: 323-328. 
  13. Suvisaari J, Perälä J, Saarni S et al. The epidemiology and descriptive and predictive validity of DSM-IV delusional disorder and subtypes of schizophrenia. Clin Schizophr Relat Psychoses. 2009; 2: 289-97. 
  14. Fenton WS, McGlashan TH. Natural history of schizophrenia subtypes. I. Longitudinal study of paranoid, hebephrenic, and undifferentiated schizophrenia. Arch Gen Psychiatry. 1991; 48: 969-77. 
  15. Schatzberg AF, Cole JO, DeBattista C. (2010). Manual of clinical psychopharmacology (7th ed.). Washington, DC: American Psychiatric Association. 
  16. Nisbet B, Dulmus C, Greyber L et al. The spectrum clozaril clinic: A successful model for treatment of psychotic disorders. Best Pract Ment Health. 2010; 6: 69-84. 
  17. Dickson RA, Dalby JT, Williams R et al. Hospital days in clozapine-treated patients. Can J Psychiatry. 1998; 43: 945-948. 
  18. Jafari S, Fernandez-Enright F, Huang X. Structural contributions of antipsychotic drugs to their therapeutic profiles and metabolic side effects. J Neurochem. 2012; 120: 371-84. 
  19. Gardner K, Bostwick J. Antipsychotic treatment response in schizophrenia. Am J Health Syst Pharm. 2012; 69: 1872-1879. 
  20. Conley RR, Kelly DL. Current status of antipsychotic treatment. Curr Drug Targets CNS Neurol Disord. 2002; 1: 123-128. 
  21. Guo X, Fang M, Zhai J et al. Effectiveness of maintenance treatments with atypical and typical antipsychotics in stable schizophrenia with early stage: 1-year naturalistic study. Psychopharmacology (Berl). 2011; 216: 475-484. 
  22. College of Psychiatric and Neurologic Pharmacists. 2010-2011 BCPP examination review and recertification course. Orth-McNeil Jansseen Scientific Affairs, LLC. 2010.
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