SCHIZOPHRENIA

SCHIZOPHRENIA

• characterized by delusions, hallucinations, disorganized thinking and speech, abnormal motor behavior, inappropriate affect, negative symptoms (normal person meron, pero sila wala), and impaired psychosocial functioning (may naririnig na mga boses)

• ⬆ Increased ventricular size and ⬇ decreased gray matter in the brain, have been reported.

• Schizophrenia causation theories include:

  • genetic predisposition (Schizophrenia can pass through genetics, so its Hereditary) , obstetric complications (⬇ oxygen supply in the brain) with hypoxia, increased neuronal pruning, immune system abnormalities, neurodevelopmental disorders, neurodegenerative theories, dopamine receptor defect, and regional brain abnormalities including hyper- or hypo-activity of dopaminergic processes in specific brain regions

PATHOPHYSIOLOGY

• may be more closely associated with dopamine receptor hyperactivity in the mesocaudate

Positive symptoms

• may be more closely associated

• may be most closely related to dopamine receptor hypofunction in the prefrontal cortex.

• Negative and cognitive symptoms

  • may be most closely related to

• A deficiency of glutamatergic activity produces symptoms similar to those of dopaminergic hyperactivity and possibly schizophrenic symptoms

• Glutamatergic dysfunction.

hallucinations

• (especially hearing voices);

• (fixed false beliefs);

delusions

ideas of influence

•  (actions controlled by external influences);

disconnected thought processes

• (loose associations); mabilis may disconnect from one topic to another

ambivalence

• (contradictory thoughts); flat, inappropriate, or labile affect; no emotion

autistic thinking

•  (withdrawn and inwardly directed thinking)

Positive symptoms:

• delusions, disorganized speech (association disturbance), hallucinations, behavior disturbance (disorganized or catatonic), and illusions.

Negative symptoms

• alogia (poverty of speech), avolition, flat affect (lack of motivation or ability to the task), anhedonia, and social isolation.

Cognitive dysfunction

• impaired attention, working memory, and executive function.

For at least 1 month, there must be at least two of the following present for a significant portion of time: delusions, hallucinations, disorganized speech, grossly disorganized or catatonic behavior, and negative symptoms. At least one symptom must be delusions, hallucinations, or disorganized speech

Criterion A

• Significantly impaired functioning.

Criterion B

The goal is to alleviate target symptoms, avoid side effects, improve psychosocial functioning and productivity, achieve compliance with the prescribed regimen, integrate the patient back into the community, prevent relapse, and involve the patient in treatment planning

TREATMENT

• perform a mental status examination, physical and neurologic examination, complete family and social history, psychiatric diagnostic interview, and laboratory workup

  • (complete blood count [CBC], electrolytes, hepatic function, renal function, electrocardiogram [ECG], fasting serum glucose, serum lipids, thyroid function, and urine drug screen).

Before treatment,

• Second generation antipsychotics (SGAs)

may have superior efficacy for negative symptoms and cognition, but this is controversial.

SGAs

• cause few or no acutely occurring extrapyramidal side effects, and to have enhanced efficacy for negative and cognitive symptoms, minimal or no propensity to cause tardive dyskinesia (TD), and less effect on serum prolactin than the first-generation antipsychotics (FGAs) (typical antipsychotics).

Clozapine

• only SGA that fulfills all the criteria

SGAs

less neurologic side effects, especially effects on movement, but they have increased risk for metabolic side effects, including weight gain, hyperlipidemias, and diabetes mellitus

• initiate antipsychotic dosing at the lower end of the dosing range.

first-episode schizophrenia,

Long-acting risperidone injection

• more effective than oral risperidone in preventing relapse over a 1-year period

Negative symptoms

• generally less responsive to antipsychotic therapy.

• Usually when taking antipsychotic medication, this is the reason why they discontinue the medication. Usually when taking antipsychotic medication there is a flare up of anxiety, according to a study, the cortisol during the time when taking this medications. The Corticotrophin Releasing Hormone, which activates the Cortisol also ⬆ increases during the time that the body adjusting to the steady state concentration of the medication, that is why if there is an increase ⬆ in the corticotropin releasing hormone, wherein the Cortisol will be activated. Remember that the Cortisol is for the fight and flight response there would be an increase episode of anxiety. But when the px already reach the steady state concentration more likely the anxiety effect decrease 

An initial dysphoric response

• The goals during the first 7 days are decreased agitation, hostility, anxiety, and aggression and normalization of sleep and eating

• Titrate over the first few days to an average effective dose. Titrate iloperidone and clozapine more slowly due to risk of hypotension.

  • If there is no improvement within 2 weeks at a therapeutic dose, then an alternative antipsychotic should be considered

• Rapid titration of antipsychotic dose is not recommended

INITIAL THERAPY

• (eg, aripiprazole 5.25-9.75 mg, ziprasidone 10-20 mg, olanzapine 2.5-10 mg, or haloperidol 2-5 mg)

IM lorazepam, 2 mg, as needed for agitation added to the maintenance antipsychotic is a rational alternative to an injectable antipsychotic

• Intramuscular antipsychotic administration can be used to calm agitated patients

Combining IM lorazepam with olanzapine or clozapine

•  not recommended because of the risk of hypotension, central nervous system (CNS) depression, and respiratory depression.

• During weeks 2 and 3, the goal is to improve socialization, self-care, and mood.

  • Improvement in formal thought disorder may require an additional 6 to 8 weeks.

• Dose titration may continue every 1 to 2 week as long as the patient has no side effects.

  • If the patient begins to show an adequate response at a particular dose, then continue at that dosage as long as symptoms continue to improve.

STABILIZATION THERAPY

• Only clozapine has shown superiority over other antipsychotics in randomized trials for treatment-resistant schizophrenia

  • Mood stabilizers (eg, lithium, valproic acid, and carbamazepine) may improve labile affect and agitation

Selective serotonin reuptake inhibitors (SSRIs) may improve obsessive- compulsive symptoms that worsen or arise during clozapine treatment

MANAGEMENT OF TREATING RESISTANT SCHIZOPHRENIA

clozapine

• shown superiority over other antipsychotics in randomized trials for treatment-resistant schizophrenia

•  (eg, lithium, valproic acid, and carbamazepine) may improve labile affect and agitation

Mood stabilizers

Selective serotonin reuptake inhibitors (SSRIs)

• may improve obsessive- compulsive symptoms that worsen or arise during clozapine treatment

• Anticholinergic side effects, most likely to occur with low potency FGA, clozapine, and olanzapine, include impaired memory, dry mouth, constipation, tachycardia, blurred vision, inhibition of ejaculation, and urinary retention.

• Elderly patients are especially sensitive to these side effects.

ADRs

Dystonias

Akathisia

EXTRAPYRAMIDAL SYSTEM

Dystonias

• prolonged tonic muscle contractions, (occurring usually within 24-96 hours of dosage initiation or dosage increase)

• Benztropine, benzodiazepines., anticholinergics, diphenhydramine (since its also has anticholinergic effect, the px fell asleep)

Dystonias tx

Akathisia

• condition that causes a feeling of restlessness and an urgent need to move.

• Symptoms include subjective complaints (feelings of inner restlessness) and/or n objective symptoms (pacing, shifting, shuffling, or tapping feet).

Akathisia symptoms

• aripiprazole and risperidone, quetiapine and clozapine

Akathisia tx

PSEUDOPARKINSONISM

• Akinesia, bradykinesia, or decreased motor activity, including mask-like facial expression, micrographia

Tremor

Rigidity

PSEUDOPARKINSONISM

Tremor

• predominantly at rest; decreasing with movement

Rigidity

• stiffness; cogwheel rigidity is seen as the patient’s limbs yield in jerky, ratchet-like fashion when moved passively by the examiner

Benztropine, diphenhydramine, amantadine, Rotigotine

Rigidity tx

TRADIVE DYSKINESIA

• abnormal involuntary movements, occurs with chronic antipsychotic therapy

• Short term treatment of TD with clonazepam or ginkgo biloba.

• Valbenazine (Ingrezza®) for the treatment of adults with TD

TRADIVE DYSKINESIA tx

• Administration of most or the entire antipsychotic daily dose at bedtime can decrease daytime sedation and may eliminate the need for hypnotics

SEDATION AND COGNITION

• chlorpromazine or clozapine

• The highest risk for antipsychotic-induced seizures is with

• risperidone, thioridazine, haloperidol, pimozide, trifluoperazine, and fluphenazine may be considered

SEIZURES

If a change in antipsychotic therapy is required,

Bromocriptine

• reduces rigidity, fever, or CK levels in up to 94% of patients.

Amantadine

• has been used successfully in up to 63% of patients.

Dantrolene

• has been used with favorable effects on temperature, heart rate, respiratory rate, and CK in up to 81% of patients

• Ziprasidone, thioridazine, Iloperidone, High IV doses of haloperidol

• QT interval prolongation

• Some SGAs and phenothiazines cause elevations in serum triglycerides and cholesterol.

• Also the reason why some of the anti psychotic increase the weight of the px

• Check the Liver function and Cholesterol called the Lipid profile (include Triglycerides, HDL, LLP & Cholesterol) Cholesterol and Triglycerides should be <200

LIPID EFFECT

• risperidone, ziprasidone,aripiprazole, asenapine, iloperidone, and lurasidone

LIPID EFFECT The risk for this effect may be less with

• Exacerbation of narrow-angle glaucoma can occur with use of antipsychotics and/or anticholinergics.

OPHTHALMOLOGIC EFFECTS

• chronic phenothiazine treatment, especially chlorpromazine

Opaque deposits in the cornea and lens may occur with

Thioridazine

doses greater than 800 mg daily (the recommended maximum dose) can cause retinitis pigmentosa (rare genetic disorder wherein there is a breakdown or loss of cells in the retina, that is why there have a light sensitivity, difficulty in seeing especially at night, and loss of peripheral visions)  with permanent visual impairment or blindness

• Urinary hesitancy and retention are common, especially with low-potency FGAs and clozapine, and in men with benign prostatic hypertrophy

NEUROLEPTIC MALIGNANT SYNDROME

Risperidone

• produces at least as much sexual dysfunction as FGAs,

  • but other SGAs (which have a weaker effect of prolactin) pose less risk.

• That is why other px taking antipsychotic will have ⬇ libido, or sometimes they cannot produce erection

• Antipsychotics can cause transient leukopenia (⬇low WBC) but it usually does not progress to clinical significance. Clozapine, chlorpromazine, and thioridazine have the highest risk of neutropenia (⬇ low neutrophils) 

• Agranulocytosis (⬇low of all the Granulocytes like Neutrophils, Eosinophilis, Basophilis) : Chlorprazine and Thioridazine

  • The onset is usually within the first 8 weeks of therapy

HEMATOLOGIC SYSTEM

Ziprasidone

• can cause a rare but fatal skin reaction called Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS).