Medically reviewed on Sep 7, 2017 by L. Anderson, PharmD.
What is Schizophrenia?
Schizophrenia is one of the most disabling medical conditions, and according to the World Health Organization (WHO), is considered a top ten illness contributing to the global burden of disease.
Schizophrenia is a "psychotic" disorder, but having psychosis does not mean you have schizophrenia. Psychosis is a symptom of other mental disorders, too. Psychosis can be defined as the inability to recognize reality.
Individuals who have schizophrenia find it difficult to tell the difference between real and unreal experiences, to think logically, to have normal emotional responses to others, and to behave normally in social situations. Hallucinations (false perceptions), delusions (false beliefs), extremely disordered thinking and speech, and inappropriate behavior can hinder daily functioning and the ability to work. Despite the perception of the general population, someone with schizophrenia is usually not aggressive and rarely poses a threat to the safety of others.
Schizophrenia is thought to affect around 1% of the population worldwide, and approximately 2.4 million American adults (about 1.1% of the U.S. population age 18 and older) are affected by schizophrenia in a given year. It is a chronic, lifelong disease that can be debilitating and requires ongoing and medically monitored treatment.
What Causes Schizophrenia?
Schizophrenia is a complex illness. Some researchers think that the brain may not be able to process information correctly. A combination of genetics, environment, and altered chemistry may contribute to its development.
- Genetics: Genetic factors appear to play a role as people who have family members with schizophrenia may be more likely to get the disease themselves. But not all people with schizophrenia have a family member with the disease.
- Environment: Some researchers also believe that events in a person's environment can trigger schizophrenia. For example, problems during intrauterine development (infection) and birth may increase the risk for developing schizophrenia later in life.
- Brain chemistry or structures: Hormonal changes, or alterations in brain neurotransmitters like dopamine or glutamate may be involved.
Psychological and social factors may also play some role in its development. However, the level of social and familial support appears to influence the course of illness and may be protective against relapse.
Who is at Risk for Schizophrenia?
Schizophrenia appears to occur in slightly higher rates among men than in women (ratio of 1.4 to 1, respectively), but women have a later onset. Schizophrenia often first appears in men in their late teens or early twenties; for women onset is usually in their late twenties or early thirties. Males therefore tend to account for more than half of patients in services; there is a high proportion of young adults. However, cases of late onset of the disorder (in individuals aged over 45 years) are known.
Childhood-onset schizophrenia can also begin after the age of 5 and, in most cases, after relatively normal development; but childhood schizophrenia is rare and can be difficult to differentiate from other pervasive developmental disorders of childhood, such as autism.
Genetic information cannot currently be used to determine one's risk for schizophrenia.
What Are the Symptoms of Schizophrenia?
People with schizophrenia may show a variety of symptoms.
Usually the illness develops slowly over months or even years. At first, the symptoms may not be noticed. For example, people may feel tense, may have trouble sleeping, or have trouble concentrating. They become isolated and withdrawn and they do not make or keep friends.
As the illness progresses, psychotic symptoms develop. The symptoms of schizophrenia fall into three major categories: positive, negative, and cognitive.
Positive Symptoms: psychotic behaviors not normally seen in healthy individuals; patients may "lose touch" with reality.
- Delusions - false beliefs or thoughts with no basis in reality. An example might be thinking that impending harm or death may occur, that one is famous or loved by a celebrity, or beliefs that aliens are inhabiting one's house.
- Hallucinations - hearing (auditory), seeing (visual), feeling (somatic), smelling (olfactory), or tasting (gustatory) things that are not there. Hearing is the most common form of hallucination, occurring in 40 to 80% of people.
- Disordered thoughts and speech - thoughts "jump" between completely unrelated topics. The person may talk nonsense or answer questions with seemingly unrelated words.
- Disordered motor behavior - bizarre motor behavior marked by a decrease in reactivity to the environment or hyperactivity that is unrelated to a stimulus. Their appearance or mood may show no emotion. Behavior can be childlike or agitated.
Negative Symptoms: a disturbance of a patient's normal emotions and behavior. Negative symptoms can be primary or secondary. Secondary symptoms can be caused by antipsychotic medications or other environmental or mental health issues.
- Flat affect - a reduced expression of emotions expressed by decreased facial expressions, tone of voice, eye contact
- Reduced speaking - avoidance of conversation or social withdrawal
- Avolition/Apathy - a decreased initiation of goal-oriented behavior and engagement in activities; difficulty starting and continuing activities
Cognitive Symptoms: nonspecific and difficult to recognize; patients may notice a change in memory.
- Disorganization - disorganized speech, thought, and/or attention
- Attention - a trouble focusing on individual tasks
- Communications skills - lack of ability to communicate
- Memory - difficulty in understanding or remembering information to make decisions
How is Schizophrenia Diagnosed?
No one symptom is specific for schizophrenia. As outlined in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), the diagnosis of schizophrenia involves the presence of at least two of the five symptoms below which are present for a minimum of a one-month period. General symptoms should have been present for at least 6 months. Delusions, hallucinations or disorganized speech must be one of the symptoms:
- Disorganized speech
- Highly disorganized or catatonic motor behavior
- Negative symptoms
In addition, a decreased level of functioning at work, interpersonal relationships, or self-care must be present.
It is important to differentiate symptoms and rule out other psychotic conditions with similar symptoms to schizophrenia, such as:
- Schizoaffective disorder
- Schizophreniform disorder
- Major depressive disorder with psychotic features
- Bipolar disorder with psychotic features
- Body dysmorphic disorder
- Post-traumatic distress disorder
- Substance abuse disorders
Patients with schizophrenia may also exhibit co-morbid conditions that occur at the same time as schizophrenia, including: panic disorder, anxiety, major depressive disorder and obsessive compulsive disorder.
Substance abuse is common in patients with schizophrenia, including alcohol, tobacco, illicit and prescription drugs. Patients have a general unawareness of their disease, which may set them up for non-adherence and poor follow-up with their healthcare provider. Poor personal hygiene and lack of social interaction can worsen clinical outcomes.
What Are the Treatment Options for Schizophrenia?
During an acute episode of schizophrenia, hospitalization is often required to promote safety, and to provide for the person's basic needs such as food, rest, and hygiene. Medications, counseling, and family support are all components of treatment. Nonetheless, relapse rates are high in patients with schizophrenia and clinical follow-up, and family or community support, when available, are important to the patient's outcome.
When possible, and prior to treatment, patients should be first assessed for ongoing movement disorders, symptoms of metabolic syndrome, and for history of cardiac disease, especially if using an antipsychotic that prolongs the QT interval.
Antipsychotic medications work by changing the balances of chemicals in the brain and are used to control the symptoms of the illness. These are considered first-line agents in schizophrenia and are the central component of the treatment, both for the acute and maintenance phase. They are usually taken in pill or liquid form, but long-acting injections that are given once or twice a month, or even every 2 months, are also options. Medications are typically continued indefinitely at the lowest possible dose to help prevent a return of symptoms.
These medications are essential but they are also associated with many side effects that may discourage a patient from taking them regularly. In fact, non-adherence with medications can occur in over 50% in patients with schizophrenia. Many of these side effects can be addressed, or will subside with time, and they should be proactively managed by the clinician.
Choice of medication is usually made based on medical status and recognition of the individual side effect profile of each agent. In general, one agent is not superior over the other with the exception of clozapine for refractory schizophrenia.
Changing to a different antipsychotic may help to manage side effects but may not necessarily boost effectiveness. Long-acting agents may be an option for patients with significant non-adherence. However, if non-adherence is due to side effects, switching to another agent with a more favorable side effect profile should be considered first.
List of Antipsychotics
Second Generation Antipsychotics
Second generation antipsychotics, also known as atypical antipsychotics, are the newer generation of antipsychotic treatment, although they have been available since the 1990's. Different neuroreceptor binding profiles include serotonin, dopamine, adrenergic, cholinergic (muscarinic), and histamine receptors. Neuroreceptor profiles can help to define side effects of the individual agents and direct prescribing based on relative risk of a particular side effect.
Second generation agents are usually preferred over the older first generation (or typical) antipsychotics because they are less likely to produce movement disorders known as extrapyramidal side effects (EPS), which includes dystonia, akathisia, pseudoparkinsonism, and potentially irreversible tardive dyskinesia. However, metabolic effects including a significant risk of weight gain, type 2 diabetes, and elevated lipids are more common with certain second generation agents.
Clozapine may have more benefit in treatment-resistant patients and in patients at risk of suicide, extrapyramidal symptoms, or tardive dyskinesia; however, there is a risk of an uncommon but severe neutropenia (previously called agranulocytosis), a serious condition of an abnormally low number of neutrophils (white blood cells or leukocytes) that are important in fighting infection. Severe neutropenia can led to a elevated risk of serious infections and death. The risk appears greatest during the first 18 weeks of clozapine treatment.
As reported in the NEJM, the incidence of agranulocytosis with clozapine was 0.80 percent at 1 year and 0.91 percent at 1.5 years. Because of the risk of severe neutropenia, clozapine is available only through a restricted program under a Risk Evaluation Mitigation Strategy (REMS) called the Clozapine REMS Program.
First Generation Antipsychotics
|Generic Name||Brand Name(s)|
|chlorpromazine||Thorazine (brand discontinued in US)|
|fluphenazine||Prolixin (brand discontinued in US)|
|haloperidol||Haldol (brand discontinued in US)|
|loxapine||Loxitane (brand discontinued in US)|
|mesoridazine (generic discontinued in US)||Serentil (brand discontinued in US)|
|molindone||Moban (brand discontinued in US)|
|perphenazine||Trilafon (brand discontinued in US)|
|thioridazine||Mellaril (brand discontinued in US)|
|trifluoperazine||Stelazine (brand discontinued in US)|
First generation antipsychotics reduce dopaminergic neurotransmission by blocking D2 receptors, and differ in level of side effects compared to first generation agents. First generation agents are classified as the phenothiazines, the thioxanthenes, and miscellaneous agents such as haloperidol and loxapine.
First generation antipsychotics are more commonly linked with extrapyramidal symptoms. Second generation antipsychotics have a somewhat better safety profile regarding side effects overall, and, in general, are preferred first-line agents due to this reason.
Possible Side Effects With Antipsychotics
- Weight gain
- Elevated blood sugar, type 2 diabetes
- Elevated cholesterol and triglycerides
- Extrapyramidal symptoms (movement disorders): acute dystonic reactions, akinesia, akathisia (restlessness), Parkinson-like symptoms, tremor, tardive dyskinesia (abnormal, repetitive facial movements)
- Prolactin elevation (hyperprolactinemia)
- Anticholinergic side Effects
- Orthostatic hypotension
- QTc prolongation
- Sexual dysfunction
- Increased risk of heat stroke
- Neuroleptic malignant syndrome
- Psychiatric side effects such as confusion, disorientation, delirium, psychosis
- Neutropenia/agranulocytosis (high risk with clozapine)
- Photosensitivity, elevated risk for sunburn
Learn More: Detailed List of Side Effects Associated with Antipsychotics
While drug treatment is the backbone of treatment for schizophrenia, nonpharmacologic, psychosocial treatments can lower hospitalizations, boost medication adherence, maintain clinic follow-up, and help prevent relapse. Individual, group, and cognitive behavioral therapy have all been used. Family support and education can also play a beneficial role.
Supportive and problem-focused forms of psychotherapy may be helpful for many individuals. Behavioral techniques, such as social skills training, can be used in a therapeutic setting or in the patient's natural environment to promote social and occupational functioning.
Family interventions that combine support and education about schizophrenia can help families cope and reduce relapse. Patients who lack family and social support may be helped by intensive case management programs that emphasize active outreach and linkage to a range of community support services.
Community rehabilitation services may include:
- Case management
- Self-help groups
- Drop-in community centers
- Housing support
- Employment programs
- Counseling and talk therapy
- 24-hour crisis services
How Can You Help Someone with Schizophrenia?
The role of a caretaker for someone with schizophrenia can be difficult. Remember that schizophrenia is a biological illness and treatment can have a positive effect. Work with the doctor if you are a caretaker, and also remember to take time to find services to support your role, too. Here are other suggestions:
- Initiate treatment at a doctor's office
- Encourage ongoing treatment
- Help with transportation to clinic visits, if and when able
- Learn how to monitor symptoms and report side effects when suspected
- Be respectful but do not tolerate dangerous or inappropriate behavior; seek help from a medical professional in these cases
- Locate support groups in your local area
Patients - Call your doctor if:
- Voices are telling you to hurt yourself
- You are unable to care for yourself
- You are feeling hopeless and overwhelmed
- You feel like you cannot leave the house
- You are seeing things that aren't really there
- Murray CJL, Lopez AD. The Global Burden of Disease, Harvard University Press, Cambridge, MA 1996.
- Solmi M, Murru A, Pacchiarotti I, et al. Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review. Ther Clin Risk Manag. 2017; 13: 757–777. Accessed August 28, 2017 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5499790/
- Fischer B, Buchanan R, et al. Schizophrenia in adults: Epidemiology and pathogenesis. Up to Date. Updated: Mar 17, 2017. Accessed August 21, 2017 at https://www.uptodate.com/contents/schizophrenia-in-adults-epidemiology-and-pathogenesis
- Patel KR, Cherian J, Gohil K, at al. Schizophrenia: Overview and Treatment Options. Pharmacy and Therapeutics. 2014;39(9):638-645.
- Guzman F, Farinde A. First-Generation Antipsychotics: An Introduction. Psychopharmacology Institute. Accessed August 25, 2017 at https://psychopharmacologyinstitute.com/antipsychotics/first-generation-antipsychotics/
- National Institute of Mental Health (NIMH). Schizophrenia. Accessed August 25, 2017 at https://www.nimh.nih.gov/health/topics/schizophrenia/index.shtml
- Alvir J, Lieberman J, Safferman A et al. Clozapine-Induced Agranulocytosis -- Incidence and Risk Factors in the United States. N Engl J Med 1993; 329:162-167. DOI:10.1056/NEJM199307153290303. Accessed September 7, 2017 at http://www.nejm.org/doi/full/10.1056/NEJM199307153290303#t=article