Schizophrenia is a mental illness that is catastrophic in respect to its debilitating features. It has “positive” symptoms of hallucinations, delusions, and disorganized thinking; “negative” symptoms of withdrawal; cognitive symptoms of impaired memory, learning, understanding, and problem-solving; and emotional symptoms that include depression, anxiety, and suicidal tendencies.
What is the logic in treating schizophrenia?
Since it is a genetic disorder that involves variations in neurotransmitters, with the most important one being dopamine, medications that alter dopamine as well as glutamate, GABA, and acetylcholine are the cornerstone of therapy.
Messing with neurotransmitters is serious business, which means that medications that manipulate them offer great promise as well as serious side effects. Nevertheless, no one wants to go back to the days before 1950 when psychiatric facilities were nothing more than prisons. When Thorazine (chlorpromazine) was discovered in 1951, these facilities emptied, and the new age of compassionate psychiatric treatment began.
Risk versus benefit is a common consideration for medical practitioners when deciding what medication to prescribe, but when psychiatric medications—even with their risks—are considered, the devastation of schizophrenia makes treatment mandatory.
What are the risks of the antipsychotics?
- Weight gain: All patients on antipsychotics can experience an increase in their BMI due to hyperglycemia.
- Diabetes: This is a natural complication of a higher BMI and the associated hyperglycemia.
- High cholesterol
- Prolactin elevation: Prolactin is the milk letdown hormone made in the pituitary gland. It may result in galactorrhea (milk secretion) and menstrual dysfunction/infertility in women and gynecomastia (breast enlargement) and sexual dysfunction in men.
- Anticholinergic side effects: Since acetylcholine is a parasympathetic neurotransmitter impacted by the antipsychotics, an anticholinergic syndrome can occur, highlighting how this neurotransmitter works. Such interference with acetylcholine can cause the following:
- Involuntary muscle movements in the GI tract, lungs, and bladder.
- Dry mouth, constipation, decreased sweating, and blurred vision all due to fluid changes.
- Mental impairment, including to the memory, so the anticholinergic antipsychotics are not good for people over 65. Another disturbing reality is that cognitive function and dysfunction, already impacted in schizophrenia, can get even worse.
- Hypotension: What is meant by this is specifically “orthostatic” hypotension, when rising causes blood to pool in the lower part of the body, thereby affecting the preload back to the heart and causing the lower output of blood, which results in hypotension.
- Heart arrhythmia: In this case, what is meant is a lengthening of the EKG part that is the interval between the QRS peak and the T-wave peak, resulting in arrhythmia.
- Inconsistent absorption of the medication: Bioavailability is variable in many of the available antipsychotics, meaning that close monitoring to tweak the dosage is necessary for each patient. A dose that may work fine with one patient may not be enough (and can be considered a treatment failure) in another patient.
- Extrapyramidal signs: See below.
What are the different types of antipsychotics?
1989 is a dividing line between the first-generation antipsychotics (FGAs) and those that followed, which are the atypical antipsychotics.
There is significant common ground among the members of both the FGAs and the atypicals, making 1989 the only rational dividing line. As one would expect, however, the newer ones have less side effects, especially with extrapyramidal signs, with these signs a description based on the function of nerves in specific nerve tracts of the brain.
The typical (FGA) antipsychotics include the phenothiazine class. The following are FGAs:
- chlorpromazine (Thorazine)
- haloperidol (Haldol)
- prochlorperazine (Compro)
- fluphenazine (Prolixin)
- trifluoperazine (Stelazine)
- perphenazine (Trilafon)
- thioridazine (Mellaril)
- prochlorperazine (Compazine)
- mesoridazine (Serentil)
In the atypical class, there are the following:
- clozapine (Clozaril)
- lithium (Eskalith, Lithobid)
- Aripiprazole (Abilify)
- Risperidone (Risperdal)
- Quetiapine (Seroquel)
- Olanzapine (Zyprexa)
- pimozide (Orap)
- molindone (Moban)
- loxapine (Loxitane)
Thiothixene (Navane) is in a class by itself.
Both the FGA and the atypical classes can cause seizures in some patients, and rarely they can create a life-threatening condition called neuroleptic malignant syndrome, which involves fever, rigidity, mental changes, and instability of life signs.
What are extrapyramidal (phenothiazine) signs?
- Akathisia: Restlessness of movement.
- Parkinsonism: Stiff facial expression, tremor at rest, shuffling gait, and slow movements (bradykinesia).
- Dystonia: Involuntary contractions of muscle groups.
- Tardive dyskinesia (TD): Involuntary movements such as lip smacking, sucking, tongue movements, facial grimace, jaw movements, and abnormal limb or trunk movements. TD can last years.
Is there a methodology in choosing the right antipsychotic?
Each presentation of schizophrenia is unique, exhibiting an overlap of symptoms and comorbidities. The bases upon which schizophrenia is treated includes the following:
- Treating acute or chronic schizophrenia: Schizophrenia comes in stages. There is an acute phase and a chronic phase. Different drugs are used for these, including, if necessary, a second antipsychotic. The transition from acute to chronic can offer some confusing challenges.
- Positive, negative, cognitive, or emotional symptoms: The administering of drugs begin or are exchanged based on the range of symptoms—positive, negative, cognitive, and emotional. Different drugs target different symptoms preferentially.
- Comorbidities: Additional problems like depression and anxiety can be treated with their respective medications.
What if therapy doesn’t work?
Treatment failures are referred to as treatment-resistant schizophrenia. Fortunately, there are strategies for choosing alternate therapies between classes of antipsychotics. It can be challenging, but not impossible.
Treatment of schizophrenia, historically, has ranged from executions and exorcism to maintenance incarceration to Thorazine and the antipsychotics that followed. Today, many schizophrenic patients live active, functional lives, dodging the side effects of their medications but better off because of them.