How Do Second Generation Antipsychotics Work?

Second generation antipsychotics (SGAs), also known asatypicalantipsychotics, are a newer class ofantipsychoticmedications used to treat schizophrenia,bipolar disorderand related psychiatric conditions. Second generation antipsychotics were developed to improve upon the efficacy and safety of first generation antipsychotics (FGAs).

Second generation antipsychotics work by blocking the excitatory activity ofdopamineandserotonin, chemicals (neurotransmitters) released by nerve cells (neurons) to transmit nerve signals. Dopamine and serotonin regulate many functions including pleasure sensation, mood, behavior, learning and memory, among others.

While most FGAs block only D2 dopamine receptors, SGAs block both D2 receptors and 5-HT2A serotonin receptors. Receptors are protein molecules on the surface of neurons that initiate action when stimulated by these neurotransmitters. D2 and 5-HT2A receptors are types of excitatory receptors, believed to be involved inpsychosis.

Some SGAs work by also stimulating 5-HT1 serotonin receptors, which are inhibitory receptors, in addition to blocking 5-HT2A receptors. SGAs also have effects on other neurotransmitters such asnorepinephrine.

Second generation antipsychotics have a lower risk forneurologicalmovement disorders known as extrapyramidal symptoms, which are the most common side effects associated with FGAs. SGAs, however, are associated with a higher risk for metabolic side effects such as weight gain, increase inblood glucoseand cholesterol levels.

Both FGAs and SGAs are effective for the treatment of schizophrenia’s positive symptoms such as hallucinations and delusions. However, there is no evidence that SGAs have more efficacy than FGAs in alleviatingcognitiveand negative symptoms such as apathy and social withdrawal.

Second generation antipsychotics may be administered as:

• Oral: Tablets, capsules, solutions, suspensions, orsublingualtablets (placed under the tongue)
• Transdermal: Skin patches
• Injections:Intramuscularor subcutaneous

Second generation antipsychotics are used to treat the following conditions:

FDA-approved:

• Schizophrenia
• Schizoaffective disorder
• Bipolar I disorder,mania, depression and mixed episodes
• Bipolar I disorder maintenance
• Major depressive disorder
• Autism
• Tourette syndrome (a nervous system disorder involving repetitive movements or unwanted sounds)
• Agitation associated with schizophrenia and bipolar I mania
• Parkinson diseasepsychosis

Off-label uses:

• Chemotherapyassociated nausea or vomiting
• Stuttering
• Alcohol dependence
• Insomnia
• Psychosis or agitation related to Alzheimer’sdementia
• Posttraumatic stress disorder (PTSD)

Orphan designation:

• N-glycanase 1 (NGLY1) deficiency

Side effects of second generation antipsychotics may include the following:

• Weight gain
• Headache
• Lightheadedness
• Dizziness
• Vertigo
• 乏力
• Asthenia(weakness)
• Somnolence(drowsiness)
• Lethargy
• Sedation
• Confusion
• Agitation
• Aggression
• Insomnia
• Anxiety
• Irritability
• Anger
• Depression
• Hallucinations
• Disturbed sleep and nightmares
• Delirium
• Altered mental status
• Amnesia(memory loss)
• Schizophrenia
• Obsessive-compulsive disordersymptoms
• Pathological gambling
• Panic attack
• Suicidal ideation and attempt
• Gaitdisturbances
• 瀑布和accidental injury
• Tremor
• Nausea
• Vomiting
• Constipation
• Dyspepsia(indigestion)
• Increased appetite
• Increase in waist circumference
• Abdominal pain or discomfort
• Anorexia(loss of appetite) and weight loss
• Gastroesophageal refluxdisease (GERD)
• Gastritis
• Diarrhea
• Hyperglycemia(increased blood glucose levels)
• Increased HbA1c values
• Blood glucose fluctuation
• Diabetes mellitus
• Diabetic ketoacidosis
• Diabetic comawithketoacidosis
• Hyperinsulinemia (increase in bloodinsulinlevels)
• Hypertriglyceridemia (high triglycerides in the blood)
• Hypercholesterolemia(high cholesterol in the blood)
• Hyperprolactinemia (increase in bloodprolactinlevels)
• Elevated liver enzyme levels (ALT and AST))
• Elevated creatinine phosphokinase (CPK)
• Salivary glandswelling
• Hypersalivation (increased salivation/drooling)
• Hyperhidrosis(excessive sweating)
• Dehydration
• Excessive thirst
• Extrapyramidal symptoms, which are drug-induced movement disorders such as:
  • Akathisia
  • Dystonia
  • Dyskinesia
  • Akinesia
  • Muscle stiffness
  • Neurolepticmalignantsyndrome (rare, life-threatening reaction)
  • Parkinsonism
  • Tardive dyskinesia
• Paresthesia(prickling sensation)
• Impaired coordination
• Maskedfacies(loss of facial expressions)
• Restless leg syndrome
• AbnormalEEG
• Seizure
• Status epilepticus(a medical emergency, when a seizure lasts longer than five minutes)
• Depressed level or loss of consciousness
• Autonomic instability (dysfunction of theautonomic nervous system)
• Tachycardia(rapid heartbeat)
• Bradycardia(slow heartbeat)
• Arrhythmia(irregular heartbeat)
• Palpitations
• AbnormalECG(QT prolongation)
• Torsades de Pointes (irregular heart rhythm in which theventriclesbeat faster and out of synchronization with theatria)
• Temporary bundle branch block (block in the electrical pathway to the heart)
• First degreeatrioventricular(AV) block
• Mitral valveincompetence
• Angina pectoris(chest pain)
• Cardiomyopathy (heart muscledisease)
• Myocarditis (inflammation of heart muscle)
• Myocardial infarction(heart attack)
• Cardiac arrest
• Increaseddiastolicblood pressure
• Hypertension(high blood pressure)
• Pseudopheochromocytoma (severe paroxysmal hypertension)
• Hypotension(low blood pressure)
• Orthostatic hypotension (blood pressure drop when standing up from sitting or lying down)
• Syncope(fainting)
• Ischemicstroke
• Cerebrovascular disease
• Hyperpyrexia (fever)
• Hypothermia (drop in body temperature)
• Rhinitis(inflammation of thenasal passage)
• Nasopharyngitis (inflammation of nose and throat)
• Rhinorrhea(runny nose)
• Nasalcongestion
• Epistaxis(nasal bleeding)
• Cough
• Upper/lower respiratory tract infections
• Pneumonia
• Aspiration
• Pleural effusion (fluid aroundlungs)
• Dyspnea(shortness of breath)
• Sleep apnea
• Oral paresthesia (tingling, prickling or burning sensation)
• Oral hypoesthesia (reduced sensation or numbness)
• Circumoral edema (swelling around the mouth)
• Glossodynia (burning pain in the tongue)
• Swollen tongue
• Tongueparalysis
• Xerostomia(dry mouth)
• Dysgeusia(taste disorder)
• Dysphagia(swallowing difficulties)
• Hiccups
• Oropharyngeal pain (mouth and throat pain)
• Chokingdue to oropharyngeal muscle dysfunction
• Toothache
• Facial edema
• Pitting edema
• Periorbital edema (swelling around the eyes)
• Blurred vision
• Visual disturbances
• Narrow angleglaucoma(a condition that damages theoptic nerve)
• Accommodationdisorder (difficulty in focusing the eyes)
• Oculogyric crisis (prolonged upward deviation of the eyes)
• Ocularhyperemia (redness of eyes)
• Conjunctivitis(inflammation of theconjunctiva, the membrane over the whites of the eye and inner surface of eyelids)
• Teary eyes
• Eyedischargeand margin crusting
• Eye andeyelidswelling
• Dry eyes
• Reducedvisual acuity
• Ear pain
• Tinnitus(ringing in ears)
• Dysarthria(speech disorder)
• Stuttering
• Enuresis(尿失禁)
• Nocturnal enuresis(bedwetting)
• Pollakiuria (frequent daytime urination)
• Urinary abnormalities
• Dysuria(painful urination)
• Acuteinterstitialnephritis(在肾脏炎症)
• Kidney failure
• Hyperuricemia(excessiveuric acidin the blood)
• Hyponatremia (low sodium in the blood)
• Acute pancreatitis(inflammation of the pancreas)
• Colitis (inflammation of thecolon)
• Polyserositis (inflammation of serous membranes that line internalcavities)
• Ileus(temporary lack of intestinal muscle contraction)
• Intestinal obstruction
• Colonischemia(reduced blood supply to the colon)
• Fecaloma (impactedstool)
• Fecal incontinence
• Hepatotoxicity (toxicity to the liver)
• Hepatitis
• Hepatic steatosis(fatty liver)
• Liver scarring (fibrosis) and damage (necrosisand cirrhosis)
• Liver failure
• Musculoskeletal stiffness and pain
• Myoclonus(muscle spasms)
• Back pain
• Myalgia(muscle pain)
• Arthralgia(关节疼痛)
• Pain in extremities
• Myasthenic syndrome (group of conditions that cause muscle weakness)
• Rhabdomyolysis(breakdown ofskeletal musclecells)
• Application site reactions with transdermal patches
• Injection site reactions
• Oral ulcers, blisters and inflammation with sublingual administration
• Hypersensitivity reactions such as:
  • Rash
  • Urticaria(hives)
  • Pruritus(itching)
  • Alopecia(hair loss)
  • Erythema multiforme(round lesions like bullseye)
  • Skinpigmentationdisorder
  • Exfoliativedermatitis(redness and peeling of the skin)
  • Photosensitivity
  • Angioedema(swelling in the tissue under the skin ormucousmembranes)
  • Oropharyngeal spasm (mouth and throat spasm)
  • Laryngospasm (spasm of thelarynx)
  • Generalized exanthematouspustulosis(pustular eruptions)
  • Stevens-Johnson syndrome(a rare medical emergency with flu-like symptoms and a painful rash)
  • Drug rash witheosinophiliaand systemic symptoms (DRESS)
  • Toxicepidermalnecrolysis (a severe skin condition with widespread redness, skin cell death and exfoliation which can lead to sepsis)
  • Anaphylaxis (severe allergic reaction)
• Drug-induced systemic lupus erythematosus (SLE), anautoimmunecondition
• Vasculitis(inflammation of blood vessels)
• Leukocytoclastic vasculitis (small blood vessel inflammation)
• Blood disorders such as:
  • Leukopenia(low count ofleukocytes)
  • Neutropenia (low count of neutrophils)
  • Agranulocytosis(lowgranulocytes, immune cells with granules)
  • Anemia (reduced red blood cell count)
  • Elevated红细胞sedimentation rate(ESR)
  • Elevatedhemoglobin/hematocrit
  • Eosinophilia (high level of eosinophils, a type of immune cell)
  • Thrombocytopenia (decrease inplatelet count)
  • Thrombocytosis(excessive platelets in the blood)
  • Thrombotic thrombocytopenic purpura(a rare disorder that causes blood clots to form in small blood vessels)
• Myelosuppression (bone marrowdepression)
• Deep vein thrombosis/DVT (formation ofblood clotin deep veins, usually in the legs)
• Pulmonary embolism
• Hemorrhage
• Infections
• Sepsis
• Hypothyroidism
• Pituitary adenoma(benigntumor in thepituitary gland)
• Amenorrhea(absence of menstruation)
• Dysmenorrhea (menstrual pain and cramps)
• Breast enlargement
• Breast pain
• Vaginal discharge
• Gynecomastia (breast tissue growth in males) in children
• Galactorrhea(abnormal milk production and leakage)
• Sexual dysfunction
• Priapism (persistent and painful erection)
• Erectile dysfunction
• Retrogradeejaculation
• Ejaculation failure
• Syndrome of inappropriate antidiuretic hormone secretion (SIADH, a disorder which causeswater retention)
• Drug withdrawal effects
• Death

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Genericand brand names of second generation antipsychotic drugs include:

• Abilify
• Abilify Maintena
• Abilify MyCite
• aripiprazole
• Aristada
• Aristada Initio
• asenapine
• asenapine transdermal
• cariprazine
• clozapine
• Clozaril
• Fanapt
• Geodon
• iloperidone
• Invega
• Invega Sustenna
• Invega Trinza
• Latuda
• lurasidone
• Lybalvi
• Nuplazid
• olanzapine
• olanzapine/samidorphan
• paliperidone
• Perseris
• pimavanserin
• quetiapine
• Risperdal
• Risperdal Consta
• risperidone
• Saphris
• Secuado
• Seroquel
• Seroquel XR
• Versacloz
• Vraylar
• ziprasidone
• Zyprexa
• Zyprexa Relprevv
• Zyprexa Zydis