Consider Patient Preference when Prescribing Antipsychotics for Schizophrenia

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.