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In my understanding, many newer antipsychotics (e.g. olanzapine and quetiapine) are considered to have aan anti-depressive effect.

Olanzapine:

For olanzapine I found this on wikipedia: "it [olanzapine] is superior [to haloperidol] for the treatment of negative and depressive symptoms." 1

Quetiapine:

Is approaved by the FDA for treating Bipolar Depression2

For quetiapine I read that "antagonism of the 5HT2A receptor in the frontal cortex of the brain relieves negative symptoms."3

Why is the anti-depressive effect (relieve of negative symptoms) in the above quote stated to be archieved through contra-intuitive antagnism of the 5-HT receptor? And is the anti-depressive effect of newer antipsychotics archieved through their agonistic effects on some 5-HT receptors (5-HT5A for olanzapine4 and 5-HT1A (partial-agonist) for quetiapine56?

Is there a significant anti-depressive effect to newer antipsychotics? If yes, how is thisit explained?

References:

1 Abou-Setta AM, Mousavi SS, Spooner C, Schouten JR, Pasichnyk D, Armijo-Olivo S, et al. (August 2012). "First-Generation Versus Second-Generation Antipsychotics in Adults: Comparative Effectiveness [Internet]". PMID 23035275.

2 https://psychopharmacologyinstitute.com/publication/quetiapine-indications-fda-approved-and-off-label-uses-2112

3Dev V, Raniwalla J (October 2000). "Quetiapine: a review of its safety in the management of schizophrenia". Drug Safety. 23 (4): 295–307. doi:10.2165/00002018-200023040-00003. PMID 11051217.

4Roth BL, Driscol J. "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 14 August 2017.

5Jensen NH, Rodriguiz RM, Caron MG, Wetsel WC, Rothman RB, Roth BL (September 2008). "N-desalkylquetiapine, a potent norepinephrine reuptake inhibitor and partial 5-HT1A agonist, as a putative mediator of quetiapine's antidepressant activity". Neuropsychopharmacology. 33 (10): 2303–12. doi:10.1038/sj.npp.1301646. PMID 18059438.

6Schotte A, Janssen PF, Gommeren W, Luyten WH, Van Gompel P, Lesage AS, et al. (March 1996). "Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding". Psychopharmacology. 124 (1–2): 57–73. doi:10.1007/bf02245606. PMID 8935801.

In my understanding, many newer antipsychotics (e.g. olanzapine and quetiapine) are considered to have a anti-depressive effect.

Olanzapine:

For olanzapine I found this on wikipedia: "it [olanzapine] is superior [to haloperidol] for the treatment of negative and depressive symptoms." 1

Quetiapine:

Is approaved by the FDA for treating Bipolar Depression2

For quetiapine I read that "antagonism of the 5HT2A receptor in the frontal cortex of the brain relieves negative symptoms."3

Why is the anti-depressive effect (relieve of negative symptoms) in the above quote stated to be archieved through contra-intuitive antagnism of the 5-HT receptor? And is the anti-depressive effect of newer antipsychotics archieved through their agonistic effects on some 5-HT receptors (5-HT5A for olanzapine4 and 5-HT1A (partial-agonist) for quetiapine56?

Is there a significant anti-depressive effect to newer antipsychotics? If yes, how is this explained?

References:

1 Abou-Setta AM, Mousavi SS, Spooner C, Schouten JR, Pasichnyk D, Armijo-Olivo S, et al. (August 2012). "First-Generation Versus Second-Generation Antipsychotics in Adults: Comparative Effectiveness [Internet]". PMID 23035275.

2 https://psychopharmacologyinstitute.com/publication/quetiapine-indications-fda-approved-and-off-label-uses-2112

3Dev V, Raniwalla J (October 2000). "Quetiapine: a review of its safety in the management of schizophrenia". Drug Safety. 23 (4): 295–307. doi:10.2165/00002018-200023040-00003. PMID 11051217.

4Roth BL, Driscol J. "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 14 August 2017.

5Jensen NH, Rodriguiz RM, Caron MG, Wetsel WC, Rothman RB, Roth BL (September 2008). "N-desalkylquetiapine, a potent norepinephrine reuptake inhibitor and partial 5-HT1A agonist, as a putative mediator of quetiapine's antidepressant activity". Neuropsychopharmacology. 33 (10): 2303–12. doi:10.1038/sj.npp.1301646. PMID 18059438.

6Schotte A, Janssen PF, Gommeren W, Luyten WH, Van Gompel P, Lesage AS, et al. (March 1996). "Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding". Psychopharmacology. 124 (1–2): 57–73. doi:10.1007/bf02245606. PMID 8935801.

In my understanding, many newer antipsychotics (e.g. olanzapine and quetiapine) are considered to have an anti-depressive effect.

Olanzapine:

For olanzapine I found this on wikipedia: "it [olanzapine] is superior [to haloperidol] for the treatment of negative and depressive symptoms." 1

Quetiapine:

Is approaved by the FDA for treating Bipolar Depression2

For quetiapine I read that "antagonism of the 5HT2A receptor in the frontal cortex of the brain relieves negative symptoms."3

Why is the anti-depressive effect (relieve of negative symptoms) in the above quote stated to be archieved through contra-intuitive antagnism of the 5-HT receptor? And is the anti-depressive effect of newer antipsychotics archieved through their agonistic effects on some 5-HT receptors (5-HT5A for olanzapine4 and 5-HT1A (partial-agonist) for quetiapine56?

Is there a significant anti-depressive effect to newer antipsychotics? If yes, how is it explained?

References:

1 Abou-Setta AM, Mousavi SS, Spooner C, Schouten JR, Pasichnyk D, Armijo-Olivo S, et al. (August 2012). "First-Generation Versus Second-Generation Antipsychotics in Adults: Comparative Effectiveness [Internet]". PMID 23035275.

2 https://psychopharmacologyinstitute.com/publication/quetiapine-indications-fda-approved-and-off-label-uses-2112

3Dev V, Raniwalla J (October 2000). "Quetiapine: a review of its safety in the management of schizophrenia". Drug Safety. 23 (4): 295–307. doi:10.2165/00002018-200023040-00003. PMID 11051217.

4Roth BL, Driscol J. "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 14 August 2017.

5Jensen NH, Rodriguiz RM, Caron MG, Wetsel WC, Rothman RB, Roth BL (September 2008). "N-desalkylquetiapine, a potent norepinephrine reuptake inhibitor and partial 5-HT1A agonist, as a putative mediator of quetiapine's antidepressant activity". Neuropsychopharmacology. 33 (10): 2303–12. doi:10.1038/sj.npp.1301646. PMID 18059438.

6Schotte A, Janssen PF, Gommeren W, Luyten WH, Van Gompel P, Lesage AS, et al. (March 1996). "Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding". Psychopharmacology. 124 (1–2): 57–73. doi:10.1007/bf02245606. PMID 8935801.

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Explanation of anti-depressive effect of newer antipsychotics

In my understanding, many newer antipsychotics (e.g. olanzapine and quetiapine) are considered to have a anti-depressive effect.

Olanzapine:

For olanzapine I found this on wikipedia: "it [olanzapine] is superior [to haloperidol] for the treatment of negative and depressive symptoms." 1

Quetiapine:

Is approaved by the FDA for treating Bipolar Depression2

For quetiapine I read that "antagonism of the 5HT2A receptor in the frontal cortex of the brain relieves negative symptoms."3

Why is the anti-depressive effect (relieve of negative symptoms) in the above quote stated to be archieved through contra-intuitive antagnism of the 5-HT receptor? And is the anti-depressive effect of newer antipsychotics archieved through their agonistic effects on some 5-HT receptors (5-HT5A for olanzapine4 and 5-HT1A (partial-agonist) for quetiapine56?

Is there a significant anti-depressive effect to newer antipsychotics? If yes, how is this explained?

References:

1 Abou-Setta AM, Mousavi SS, Spooner C, Schouten JR, Pasichnyk D, Armijo-Olivo S, et al. (August 2012). "First-Generation Versus Second-Generation Antipsychotics in Adults: Comparative Effectiveness [Internet]". PMID 23035275.

2 https://psychopharmacologyinstitute.com/publication/quetiapine-indications-fda-approved-and-off-label-uses-2112

3Dev V, Raniwalla J (October 2000). "Quetiapine: a review of its safety in the management of schizophrenia". Drug Safety. 23 (4): 295–307. doi:10.2165/00002018-200023040-00003. PMID 11051217.

4Roth BL, Driscol J. "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 14 August 2017.

5Jensen NH, Rodriguiz RM, Caron MG, Wetsel WC, Rothman RB, Roth BL (September 2008). "N-desalkylquetiapine, a potent norepinephrine reuptake inhibitor and partial 5-HT1A agonist, as a putative mediator of quetiapine's antidepressant activity". Neuropsychopharmacology. 33 (10): 2303–12. doi:10.1038/sj.npp.1301646. PMID 18059438.

6Schotte A, Janssen PF, Gommeren W, Luyten WH, Van Gompel P, Lesage AS, et al. (March 1996). "Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding". Psychopharmacology. 124 (1–2): 57–73. doi:10.1007/bf02245606. PMID 8935801.