Atypical antipsychotics

Definitions & Key takeaways

Atypical antipsychotics are a newer class of medications used to treat schizophrenia and bipolar disorder. Unlike the older typical antipsychotics, atypical antipsychotics are not as likely to cause movement disorders like tardive dyskinesia. However, atypical antipsychotics can sometimes cause other side effects, such as weight gain, high blood sugar, and heart problems such as myocarditis.

Chapters:

Watch video only

Introduction0:00–0:30

Antipsychotics, as their name implies, are mainly used to treat schizophrenia and other psychotic conditions. Even though the exact cause of schizophrenia is still unknown, there's some evidence that suggests it’s related to altered levels of the neurotransmitter dopamine.
Now, antipsychotics are subdivided into two main categories: the first generation or typical antipsychotics, and the second generation or atypical antipsychotics.
Alright, within the brain, dopamine is found in 4 main dopamine pathways: the mesolimbic pathway, which controls motivation and desire; mesocortical pathway, which helps regulate emotions; nigrostriatal pathway, which contains motor neurons that bypass the medullary pyramids, to control involuntary movements and coordination; and lastly, tuberoinfundibular pathway, which releases dopamine to limit the secretion of prolactin.

Physiology0:30–1:11

Other regions of the central nervous system that are rich in dopamine receptors, include the chemoreceptor trigger zone, which initiates the vomiting reflex; and the medullary periventricular pathway, which regulates eating behavior.
However, in schizophrenia, altered levels of dopamine mainly affect the mesolimbic pathway and mesocortical pathway. There’s usually high levels of dopamine in the mesolimbic pathway, which cause positive symptoms of schizophrenia, such as delusions, hallucinations, and disorganized thought.

Pathology1:11–1:42

On the other hand, low levels of dopamine in the mesocortical pathway cause negative symptoms of schizophrenia, such as lack of motivation, social withdrawal and “flat affect”, which basically means lack of emotions.
Now, in conditions such as schizophrenia, atypical antipsychotics block dopamine D2 receptors in the mesolimbic pathway, thereby alleviating positive symptoms of schizophrenia.

Mechanism of Action1:42–2:27

But, they also block serotonin 5-HT2A receptors in the mesocortical pathway. These receptors are found on inhibitory neurons that regulate dopaminergic neurons and decrease dopamine release.
When atypical antipsychotics block them, dopaminergic neurons have no inhibitory signals, so dopamine release actually increases in the mesocortical pathway.
This will help alleviate the negative symptoms of schizophrenia which makes atypical antipsychotics the preferred medication over the older, typical antipsychotics, which only treat positive symptoms.

Indications2:27–3:15

Common atypical antipsychotics include clozapine, olanzapine, quetiapine, paliperidone, risperidone, lurasidone, ziprasidone, and aripiprazole.
Besides its effect on D2 and 5-HT2A receptors, aripiprazole partially stimulates D2 and 5-HT1 receptors. Other common indications for atypical antipsychotics include bipolar disorder, obsessive-compulsive disorder or OCD, anxiety, depression, and Tourette syndrome, which is a neurological disorder characterized by repetitive, involuntary movements and vocalizations called tics.
Moreover, atypical antipsychotics are typically used as first-line agents for the management of acute mania. Alright, moving on to side effects.

Side Effects3:15–6:19

Besides D2 receptors in the mesolimbic pathway, atypical antipsychotics also block dopamine receptors in the tuberoinfundibular pathway, causing hyperprolactinemia.
Furthermore, high levels of prolactin indirectly decrease levels of GnRH, LH, and FSH, causing oligomenorrhea, galactorrhea, and gynecomastia, which is an enlargement of the male breasts.
Risperidone is the most likely to cause hyperprolactinemia. Furthermore, atypical antipsychotics block dopamine receptors in the nigrostriatal pathway causing extrapyramidal symptoms.
These symptoms can be subdivided into 2 main groups: acute extrapyramidal symptoms, which include dystonia, akathisia, and pseudoparkinsonism, also known as drug-induced Parkinsonism; and tardive, or delayed extrapyramidal symptoms, which include tardive dyskinesia.
The most dangerous side effect is neuroleptic malignant syndrome or NMS, which is characterized by confusion, agitation, muscle rigidity, seizures, and hyperthermia.
If this condition progresses, it will turn into rhabdomyolysis, which is the breakdown of muscles. Treatment of neuroleptic malignant syndrome includes application of dantrolene, which is a muscle relaxant; and dopamine agonists, such as bromocriptine, which mimics the effect of dopamine.
Now, in contrast to typical antipsychotics, which bind very tightly to D2 receptors, atypical antipsychotics bind to D2 receptors more loosely, so they can be kicked off if there’s lots of dopamine around.
This is why they cause fewer extrapyramidal symptoms than typical antipsychotics. Besides dopamine D2 receptors and serotonin 5-HT2A receptors, atypical antipsychotics also block: histamine H1 receptors causing sedation; alpha-1 receptors, causing orthostatic hypotension; and muscarinic receptors, causing atropine-like (anticholinergic) side effects, such as dry mouth, blurred vision, urinary retention, and constipation.
Atypical antipsychotics can also cause metabolic syndrome, which includes weight gain, diabetes, dyslipidemia, and increased cardiovascular risk.
People treated with olanzapine and clozapine tend to gain the most weight, while aripiprazole has the least impact on weight.
Clozapine can also cause seizures and agranulocytosis, which is a condition where a person’s white blood cells are depleted, resulting in frequent and overwhelming infections.
Because of this, the white blood cell count (WBC) and absolute neutrophil count (ANC) need to be monitored, so it’s only used in individuals that don’t respond to other antipsychotics.
Finally, atypical antipsychotics, especially ziprasidone, can prolong the Q-T interval and should be avoided in people with arrhythmias.
Now, we want to make a simple and fun mnemonic that’ll help you efficiently memorize and retain all these pharm facts! So, just like the video for first generation, or typical antipsychotics, we’ll start with a house with an aunt inside.

Memory Palace6:19–9:51

Except this aunt is rather atypical and eccentric as represented by her rainbow afro! She also has 2 dobermans for D2 receptors, but she’s got 5 cups of hot tea for 5-HT2A receptors.
Now, one side of the room has loose electrical wires that’ll zap anyone that comes near them, so this is where we’ll put the medications that end with “zapin.” So there’s a large clothespin clamped on the wires for clozapine, and a bullfighter getting zapped and yelling “o’le” for olanzapine.
Now quetiapine doesn’t have a “Z” so we can put a quiet librarian not getting zapped going “shush” to the bullfighter. She’s got a paper airplane stuck in her hair for aripiprazole.
Now, for the medications ending in “idone” we can put them next to the TV, which is showing an episode of Antipsychotic Idol!
Watching the show, we have a pelican for paliperidone, and a raspberry for risperidone. The pelican has a zipper on his mouth to stop him from talking, which represents ziprasidone.
Now for indications, our uncle is an obsessive mad scientist, representing obsessive compulsive disorder and mania. He’s cutting a brain in half since schizophrenia literally means split mind.
One half has a + sign on it, while the other half has a - sign, since atypical antipsychotics treats both positive and negative symptoms.
Now, our uncle also has two lab assistants; one is anxiously holding the leash of a two headed polar bear, representing anxiety and bipolar disorder; the other is very sad looking, representing depression, and that’s because he only gets to take care of a tortoise, for tourette syndrome.
Okay, let’s go outside the house to look at the side effects. Our eccentric aunt built a pyramid for the extrapyramidal side effects.
It’s just like the one from the first generation antipsychotic video except it’s smaller, since these side effects are less severe for atypical antipsychotics.
Now, for the other side effects, let’s put them next to the pyramid. There’s a dizzy cow, to represent orthostatic hypotension.
There’s milk leaking out of its udders, for hyperprolactinemia. Standing by it, is an obese man eating candy bars for weight gain, hyperlipidemia, and diabetes.
Now, let’s have the raspberry man milk the cow, since risperidone is the atypical antipsychotic that’s most likely to cause this problem.
Next, let’s have the bullfighter with a clothespin on his red cape taunt the obese man. This helps you remember these two medications are the most likely to cause weight gain.
Behind him is a grain silo that’s leaking out white blood cells through a gap, for agranulocytosis. Clamped onto the silo is a clothespin, since this is a side effect specific to clozapine.
Okay, on the other side of the pyramid is a tropical palm tree, for atropine-like side effects. Under the tree is a sleeping snake going hizzzz, for sedation caused by blocking histamine receptors.
On top of the tree is a giant cute squirrel, with a long tail for Q-T prolongation. This squirrel has a long zipper on its tail since ziprasidone is the most likely atypical antipsychotic to cause this side effect.
All right, as a quick recap. Atypical antipsychotics block dopamine D2 receptors in the mesolimbic pathway, and serotonin 5-HT2A receptors in the mesocortical pathway, thereby alleviating both positive and negative symptoms of schizophrenia.

Review9:51–10:38

Common indications for atypical antipsychotics include: schizophrenia, bipolar disorder, obsessive-compulsive disorder, anxiety, depression, and Tourette syndrome.
Common side effects include: metabolic syndrome, hyperprolactinemia, extrapyramidal symptoms, sedation, orthostatic hypotension and anticholinergic side effects.
The most dangerous one, however, is neuroleptic malignant syndrome. But wait, there’s more: Here’s a mind map with all of the mnemonics.

Mind Map10:38–10:48

Go ahead and pause the video so you can test yourself to see what you remember. Stay tuned for the answers after the credits.