First versus Second-Generation Antipsychotics

First versus Second-Generation Antipsychotics

First versus Second-Generation Antipsychotics 150 150 Peter

First versus Second-Generation Antipsychotics

Please discuss the differences between first-generation antipsychotics (FGA) and second-generation antipsychotics (SGA). BE SPECIFIC and MAKE SURE TO Include relevant pharmacodynamics and pharmacokinetics and the implications of each. Include the concepts of receptor affinity, binding, and potency. You will be graded on this.

Responses must be a minimum of 150 words, scholarly written, APA formatted, and referenced. A minimum of 2 scholarly references are required (other than your text). Refer to the Grading Rubric for Online Discussion in the Course Resource section.


Stahl, S. M. (2013). Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications (4th ed.). Cambridge University Press.

Gabbard, G.O. (2014). Gabbard’s treatments of psychiatric disorders (5th ed.). American Psychiatric Publishing

American Psychological Association. (2020). Publication manual of the American Psychological Association (7th ed.).

Sample Paper

First versus Second-Generation Antipsychotics

First-generation antipsychotics (FGAs) can be referred to as an older class of antipsychotics which are also known as typical antipsychotics. On the other hand, second-generation antipsychotics (SGAs) are a newer generation of antipsychotics (APA, 2020). FGAs are typically used in the treatment of positive symptoms such as delusions and hallucinations. In contrast, SGAs are more effective in the treatment of both positive and negative symptoms of psychosis, including schizophrenia. Therefore, the negative symptoms of psychosis include the general lack of ordinary mental activities such as social engagement, emotional expression, motivation, and thinking (Stahl, 2013).

First-generation antipsychotic drugs have high potency and high affinity for dopamine receptors. FGAs typically lead to the induction of extrapyramidal side effects due to the blocking of dopamine receptors. The different types of extrapyramidal side effects include Parkinsonism which is defined by pill-rolling tremor, cogwheel muscle rigidity, and slowed or reduced movements (Gabbard, 2014). Another extrapyramidal side effect associated with FGA’s is dyskinesia which includes an involuntary repetitive and purposeless body or facial movements. First-generation antipsychotics are also associated with extrapyramidal side effects related to akathisia which includes more restlessness which resembles agitation, especially in the legs, and dystonia, which includes unusual twisting of different parts of the body and contraction, especially in the neck (Gabbard, 2014).

In contrast, SGAs usually have a low affinity for dopamine receptors while also working effectively to block serotonin receptors in a patient, which helps in lowering the risk of various extrapyramidal side effects (APA, 2020).

FGA’s can be classified as dopamine antagonists because they act on different regions such as the mesocortical, mesolimbic, tuberoinfundibular, and nigrostriatal pathways. Dopamine antagonism is the characteristic that makes SGA’s to be efficient antipsychotics. However, besides the dopamine antagonism FGAs also have an effect on other receptors such as an adrenergic, alpha-1 muscarinic, and histamine 1(Stahl, 2013). The blocking of these different receptors is therefore related to the adverse side effects profile of FGAs. In contrast, SGAs also block dopamine receptors to an extent but differ significantly from first-generation antipsychotics because of their ability to block serotonin receptors. SGAs are therefore also referred to as serotonin dopamine antagonists. Generally, SGAs Have a high affinity for serotonin receptors compared to dopamine receptors (Stahl, 2013).

Comparing the efficacy of FGAs and SGAs, different high-quality scholarly studies suggest that there is a small effect of improved overall symptoms with SGAs such as olanzapine, risperidone, and amisulpride. Most first-generation antipsychotics require the administration of a high dose to patients, which increases the chances of occurrence of adverse side effects (Gabbard, 2014). According to Stahl (2013), olanzapine and risperidone, which are second-generation antipsychotics, can improve cognition more effectively than haloperidol. Some second-generation antipsychotics have also been shown to improve the quality of life of patients better than FGAs. However, considering the available evidence that is available, there is no concrete observation that SGAs are significantly more effective than FGAs in the treatment of negative and positive symptoms of schizophrenia. However, because first-generation antipsychotics are dopamine antagonists, they will be substantially associated with a higher risk of extrapyramidal side effects (Stahl, 2013). On the other hand, second-generation antipsychotics, which are serotonin dopamine antagonists, will be associated with a lower risk of extrapyramidal side effects but a higher risk of different metabolic side effects (Gabbard, 2014).



American Psychological Association. (2020). Publication manual of the American Psychological Association (7th ed.). Manual of the American Psychological Association.

Gabbard, G. O. (2014). Gabbard’s Treatments of Psychiatric Disorders (5th ed.). Amer Psychiatric Pub.

Stahl, S. M. (2013). Stahl’s Essential Psychopharmacology: Neuroscientific Basis and Practical Applications (4th ed.). Cambridge University Press.