Typical Antipsychotics: How Do They Work?
Author:
Emma Loker
B.S
Editor:
Ashley Pena
LCSW
The mental health field has used first-generation antipsychotics (known as FGAs or typical antipsychotics) to treat psychosis since the 1950s. Since then, they’ve proved to be effective at treating a range of other psychiatric conditions. In the 1980s, a second-generation of antipsychotics was created, known as atypical (or AAPs).1
Both of these classes of drugs are widely used today. But how do they work and how do FGAs compare to AAPs?
If you’ve been prescribed an FGA, you might have lots of questions about how they’ll make you feel or what happens if you withdraw from them. On this page, we aim to inform you of all the key things to know about typical antipsychotics. We’ll explore:
What first-generation antipsychotics are used for- How first-generation antipsychotics work
- Common side effects
- How they compare to second-generation antipsychotics
- Experiencing withdrawal and long-term use
- Some other FAQs
Let’s get started!
What Are First-Generation Antipsychotics and What Are They Used For?
First-generation typical antipsychotics (FGAs) are a classification of medications that are used to treat several mental health conditions. They are approved by the U.S. U.S. Food and Drug Administration (FDA) to treat people with:
Schizophrenia and schizoaffective disorders- Acute mania
- Major depressive disorder (with psychotic features)
- Delusional disorder (could be associated with personality disorders)
- Severe agitation
- Tourette’s disorder
- Borderline personality disorder (BPD)
- Dementia and delirium
- Substance-induced psychotic disorder
- Childhood schizophrenia2
Of course, each FGA has its own applications and they have their differences. The best one for you will depend on your condition, other health circumstances, experience of side effects, and how you’ve responded to previous treatments.
When prescribing typical antipsychotics for psychosis or acute mania, all of them can be suitable. In fact, all first-generation and second-generation medications could be a first-line treatment except for Clozapine.
Symptoms of schizophrenia can be categorized into ‘positive’ (hallucinations and delusions) and ‘negative’ (being ambivalent or withdrawn). While FGAs are better at treating ‘positive’ symptoms and reducing the risk of another psychotic episode, AAPs can treat both ‘positive’ and ‘negative’ symptoms.2
When treating Tourette’s disorder, dementia, or delirium, FGAs are the first-line and most common treatment. AAPs can be used for these conditions, but it would be off-label (not officially FDA-approved).2
How Do Typical Antipsychotics Work?
When typical antipsychotics reach your brain, they partially block the actions of dopamine, a neurotransmitter involved with your mood, motivation, thinking, movement, pleasure, and more. FGAs also block action at histamine (involved with wakefulness), choline (heart rate and muscle contraction), and noradrenaline (stress response, wakefulness, mood, cognition) receptors.2
By blocking action at these sites, psychotic symptoms are reduced.2 Unfortunately, this action also comes with undesired side effects which we’ll explore now.
Side Effects of Typical Antipsychotics
If you’re prescribed first-generation antipsychotics for schizophrenia or any other condition, you’re likely to experience some form of side effect. Of course, these will vary across different medications, but many side effects are shared across antipsychotics because of the way they behave in the brain.
Typical Antipsychotics and Sedation
For example, the way in which FGAs interact with your histamine receptors (associated with your sense of wakefulness) often results in a sedative effect. You’re likely to feel tired or lacking in energy on most antipsychotics. In terms of sedation alone, Chlorpromazine (sold as Thorazine or Largactil) causes the most sedation. Meanwhile, FGAs such as Fluphenazine (Prolixin), Haloperidol (Haldol), and Pimozide (Orap) cause the least.2
Other FGA Side Effects
In addition, the way first-generation antipsychotics block choline receptors in your brain can cause side effects like dry mouth, retaining urine, and constipation. FGAs can also make it easier for your body to have seizures, make your heartbeat irregular, and cause both dizziness and lightheadedness when you sit down or stand up.2
Weight gain is a common experience for people taking antipsychotic medication, often occurring rapidly in the first few weeks of treatment. Haloperidol is one first-generation antipsychotic with the smallest risk of weight gain, though it’s still there.3
Sexual dysfunction is another common experience for people taking FGAs. This is because these drugs can increase levels of prolactin in your body, which is a hormone involved with sexual function. This increase can cause a range of symptoms including absent periods, breast enlargement and excess milk production, and the inability to or difficulty achieving orgasm in both men and women.2
Furthermore, Chlorpromazine (Thorazine or Largactil) is associated with:
-
Photosensitivity: Your skin becomes more sensitive to sunlight and can burn more easily.- Allergic dermatitis: A skin rash or irritation caused by an allergic reaction.
- Blue/gray skin discoloration: Some people may notice changes in skin color.
- Benign eye pigmentation: Changes in eye color that don’t affect your vision.2
If you’re concerned about any of these side effects, speak to your doctor. They will be able to advise you on the specific side effects of your prescription and how to manage or reduce them. It’s possible that your dose could be reduced, changed, or split across the day to make things better for you.
First-Generation Antipsychotics and EPS
A big drawback of first-generation antipsychotics is their association with significant extrapyramidal symptoms (EPS).2 These are sometimes called ‘medication-induced movement disorders’ because of the way muscles and motor functions are impacted.
Almost all antipsychotic medications cause EPS in some way, but it varies between medications and can depend on the strength of your dose. Very serious manifestations of EPS include tremors, involuntary movements (dystonia), tardive dyskinesia (facial tics), and parkinsonism.4
Fortunately, many people with EPS can be treated and will recover. This is more likely with early detection, so your doctor should monitor you for abnormal movements. If you’re experiencing EPS, it might be quickly resolved by immediately stopping or reducing your medication and receiving an injection.4
First-Generation vs Second-Generation Antipsychotics
Second-generation antipsychotics (AAPs) affect two brain chemicals: dopamine and serotonin receptors. In contrast, first-generation antipsychotics (FGAs) mostly focus on blocking dopamine.5 Because of this, AAPs can help with a wider range of symptoms – including both the “positive” symptoms (like hallucinations and delusions) and the “negative” symptoms (like lack of motivation or social withdrawal). Whereas FGAs mostly help with the positive symptoms only.2
If reducing the risk of another psychotic episode is the main priority, first-generation antipsychotics are the more effective option.2 Unfortunately, FGAs are credited with causing more adverse side effects than AAPs, particularly in relation to extrapyramidal symptoms. On the whole, this is why second-generation antipsychotics tend to be the preferred treatment.5
You’ll also want to consider the side effects. For example, when it comes to causing sexual dysfunction, many AAPs are known as ‘prolactin-sparing’ and some FGAs like Haloperidol (Haldol) are ‘prolactin-elevating’. The greater the prolactin elevation in your body, the greater the risk of symptoms of sexual dysfunction.6
When thinking about taking typical vs atypical antipsychotics, the risks must be compared with the benefits. You might prefer to take an AAP if your ‘negative’ symptoms (like being withdrawn) are a big part of your condition. However, first-generation antipsychotics are usually the cheaper option as they’ve been around for a long time.7
Withdrawal and Long-Term Use of Typical Antipsychotics
Using FGAs Long-Term
Most people with schizophrenia will benefit from taking antipsychotics long-term. However, that doesn’t mean you have to remain on typical antipsychotics forever. If you’ve evaluated your options with your doctor, you should have some second-generation antipsychotics available to you that will ideally reduce the risk of long-term side effects.8
These long-term effects of typical antipsychotics can include sedation, weight gain, disturbance to your metabolism, heart rate irregularities, and neurologic adverse effects (which can impact cognition, movement, and vision among other things).8
Understandably, these long-term impacts can be frightening. You might be weighing up the risks vs benefits of taking your medication long-term. While there are risks to your physical health, medication for your mental health can be life-changing in the most positive way.
You should know that people with schizophrenia live longer if they receive antipsychotic treatment. Untreated, their life expectancy is lower and they’re more likely to suffer other health conditions. Antipsychotic medications improve life expectancy for people with schizophrenia, despite the increased risks to their cardiovascular and metabolic health.8
Some research suggests that a small percentage of people could discontinue their antipsychotic treatment with no risk of relapsing. Things like having a partner or job, being female, living independently, not suffering from substance abuse, and experiencing schizophrenia at an older age have been identified with better outcomes for people discontinuing antipsychotic treatment.8
If discontinuing isn’t an option for you, it’s recommended that you receive other sorts of treatment alongside your medication. Cognitive-behavioral therapy (CBT), in particular, has been found to have antipsychotic effects. Combining medication with psychosocial interventions like CBT will improve the risk vs benefit ratio of taking antipsychotics long-term.8
Withdrawing From FGAs
Even though it can be a difficult experience, you have the right to withdraw from your antipsychotic medication if you want to. Stopping first-generation antipsychotics can come with varying side effects, but this can be managed by tapering off of them gradually. The slower you do so, the less noticeable the impact will be.
If you do want to discontinue your prescription, speak to your doctor about your options. Plus, don’t forget to tell your family and friends so they can support you through the process.
Sudden typical antipsychotic withdrawal can involve the following side effects:
Nausea and vomiting- Diarrhea
- Headaches
- Sweating
- Increased heart rate
- Vertigo
- Abdominal pain
- Restlessness, anxiety, and tension
- Insomnia and lower sleep quality
- Muscle aches and pains
- Dry mouth, throat, and nose
There are also isolated reports of people experiencing nightmares, numbness, runny noses, and having a bad taste in the mouth.9 Of course, you should experience fewer of these effects by withdrawing slowly.
First-Generation Antipsychotic FAQs
What’s The Safest First-Generation Antipsychotic?
All FDA-approved antipsychotics have been rigorously tested before being deemed safe and effective. You might feel safer taking one with less risk of certain side effects, but it may come with a higher risk for others. For example, Haloperidol may cause less weight gain but greater sexual dysfunction. Speak to your healthcare provider about the risks associated with your prescription.
Why Do Antipsychotics Cause Weight Gain?
Antipsychotics cause weight gain because of the way they impact the parts of your brain involved with appetite control and metabolism. If you’re worried about weight gain during your treatment, you should be given nutritional counseling as a first intervention. If you gain significant weight, your doctor may be able to reduce your dose, switch to a different antipsychotic (e.g., Haloperidol), or prescribe you something like Metformin.3
Can I Take Antipsychotics If I’m Pregnant or Breastfeeding?
It’s not advised. Typical antipsychotics should be avoided during pregnancy, particularly in the first trimester. If the benefits seriously outweighed the risks, first-generation antipsychotics could be administered during later pregnancy but this would be an extreme measure. In addition, FGAs are secreted via breast milk, making breastfeeding during treatment inadvisable.2
Who Shouldn’t Use Typical Antipsychotics?
Someone with any of the following health circumstances should avoid FGAs:
They’re taking a central nervous system depressant like opioids, barbiturates, or benzodiazepines- They have a history of severe allergies or seizures
- They have severe cardiac abnormalities (i.e., heart defects)
- They’re taking an anticholinergic medication such as scopolamine or phencyclidine
- They have narrow-angle glaucoma or an enlarged prostate
- They had or still have tardive dyskinesia (facial tics)
These conditions and medications will interact with first-generation antipsychotics in ways that could be harmful, so you should tell your doctor if any apply to you.2
Find Out More About Typical Antipsychotics at Mission Connection
To learn all about different antipsychotic medications, check out our blog. If you choose to receive mental health support from us here at Mission Connection, know that our priority is that your care is personalized. If it’s beneficial for you, we also provide talking therapies, whether it’s online, in person, or both.
Call us today to ask any questions or request a consultation, or get started online here.
References
- Abou-Setta, A. M., Mousavi, S. S., Spooner, C., Schouten, J. R., Pasichnyk, D., Armijo-Olivo, S., Beaith, A., Seida, J. C., Serdar Dursun, Newton, A. S., & Hartling, L. (2012, August). First-Generation Versus Second-Generation Antipsychotics in Adults: Comparative Effectiveness. Nih.gov; Agency for Healthcare Research and Quality (US). https://www.ncbi.nlm.nih.gov/books/NBK107237/
- Chokhawala, K., & Stevens, L. (2023, February 26). Antipsychotic Medications. National Library of Medicine; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK519503/
- Dayabandara, M., Hanwella, R., Ratnatunga, S., Seneviratne, S., Suraweera, C., & de Silva, V. (2017). Antipsychotic-associated Weight gain: Management Strategies and Impact on Treatment Adherence. Neuropsychiatric Disease and Treatment, 13(13), 2231–2241. https://doi.org/10.2147/ndt.s113099
- D’Souza, R. S., & Hooten, W. M. (2023). Extrapyramidal symptoms (EPS). Nih.gov; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK534115/
- Willner, K., Vasan, S., & Abdijadid, S. (2024, May 1). Atypical Antipsychotic Agents. PubMed; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK448156/
- Park, Y. W., Kim, Y., & Lee, J. H. (2012). Antipsychotic-Induced Sexual Dysfunction and Its Management. The World Journal of Men’s Health, 30(3), 153. https://doi.org/10.5534/wjmh.2012.30.3.153
- NIH/National Institute of Mental Health. (2006, December 1). Older Medication May Be More Cost-effective For Some Patients With Schizophrenia. ScienceDaily. Retrieved May 23, 2025 from www.sciencedaily.com/releases/2006/12/061201105955.htm
- Correll, C. U., Rubio, J. M., & Kane, J. M. (2018). What is the risk-benefit ratio of long-term antipsychotic treatment in people with schizophrenia? World Psychiatry, 17(2), 149–160. https://doi.org/10.1002/wps.20516
- Brandt, L., Bschor, T., Henssler, J., Müller, M., Hasan, A., Heinz, A., & Gutwinski, S. (2020). Antipsychotic Withdrawal Symptoms: A Systematic Review and Meta-Analysis. Frontiers in Psychiatry, 11. https://doi.org/10.3389/fpsyt.2020.569912
