Transcript: 

Psychosis is a mental condition in which a person loses touch with reality.

Positive symptoms of psychosis – reflecting abnormal additions to or distortions of otherwise normal emotional or mental function – include hallucinations, delusions, agitation, and disorganized thought and speech.

Negative symptoms reflect deficits in normal emotional function or thought processes, and include blunted affect, avolition, alogia, asociality, and anhedonia (an inability to experience pleasure).

A diagnosis of schizophrenia requires that 2 of 5 of these core symptoms must be present for at least 1 month, with a significant impact on social or occupational functioning that must persist for at least 6 months.

In healthy individuals, dopamine is synthesized in the presynaptic neuron, stored in vesicles, and released into the synapse, where it diffuses across the synaptic cleft and binds to the dopamine receptors on the postsynaptic neuron.

In patients with schizophrenia, psychotic symptoms are caused by dysregulated dopamine signaling. The volume of dopamine entering the synapse and bombarding the receptors is greater than in healthy individuals. Higher dopamine levels in the caudate nucleus are thought to cause positive symptoms.

Concurrently, hypoactive dopaminergic activity in the mesocortical pathway can cause negative symptoms. 

The distribution of opposing excesses and deficits of dopaminergic neurotransmission explains the co-occurrence of positive and negative symptoms in the same patient.

The American Psychiatric Association states that there is currently no way to reliably predict a patient’s response or toleration of one antipsychotic relative to another.

Currently available antipsychotic agents include first-generation (or typical) antipsychotics and second-generation (or atypical) antipsychotics.

Both typical and atypical antipsychotics block dopamine receptors along the mesolimbic pathway, relieving positive symptoms.

However, more rapid dissociation of atypical agents from the D2 receptor reduces the risk of extrapyramidal symptoms compared with the typical agents. 

Atypical agents also target serotonin receptors in the brain, which may potentially alleviate negative symptoms and further reduce the risk of extrapyramidal symptoms.

Dopaminergic adverse effects of antipsychotics include extrapyramidal effects such as akathisia and parkinsonism, hyperprolactinemia, and metabolic effects such as hyperglycemia and dyslipidemia.

Adverse events also occur through peripheral effects of antipsychotics.

Histaminergic effects include sedation and weight gain.

Alpha-adrenergic effects include orthostatic hypotension, changes in heart rate and pulse.

Cholinergic effects include dry mouth and blurred vision.

Other serious potential adverse effects with certain antipsychotic medications may include QT prolongation, lower seizure thresholds in patients with seizure disorders, and neuroleptic malignant syndrome, a rare but potentially fatal event.

Selection of an antipsychotic agent will be based on:

• A discussion with the patient about potential benefits and side effects

• Patient preference

• Previous treatment response

• Comorbidities that may be affected by specific side effects

• Available formulations

• Drug interaction potential; and An agent’s receptor binding profile.

• For inpatients who do not respond to an antipsychotic after a trial of at least 6 weeks:

• The diagnosis may be reconsidered

• The patient may be switched to another antipsychotic, and/or

• Combination therapy may be an option

For nonadherent outpatients, steps should be taken to ensure adherence, including perhaps prescribing a long-acting injectable antipsychotic

Clozapine can be considered after failure with 2 antipsychotics, but this agent sees limited use due to serious potential adverse effects.

Treatment-resistant patients may benefit from adjunctive electroconvulsive therapy 

Ultimately, the goal of acute treatment with an antipsychotic medication is to not only reduce or eliminate acute symptoms, but also to return the patient to the level of functioning they had prior to symptom onset.

Upon achieving the best possible control of symptoms and implementing a multidisciplinary care plan, maintenance antipsychotic drug therapy with continuing support from family and friends will help prevent recurrences of symptoms, preserve function, and maintain the patient’s quality of life.