Review
Copyright ©The Author(s) 2024.
World J Psychiatry. Jun 19, 2024; 14(6): 767-783
Published online Jun 19, 2024. doi: 10.5498/wjp.v14.i6.767
Table 1 Commonly used antipsychotic drugs and antidepressants, main mechanism of action and weight gain
Antipsychotic drugs
Main mechanism of action[23-25]
Main mechanism of action[28,29]
Weight gain[8,26,27]
Weight gain[31,32]
Typical APs
ChloropromazineBlocks post-synaptic dopamine D2 receptors in the brain+++
HaloperidolBlocks post-synaptic dopamine D2 receptors in the brain+
ThiothixeneBlocks post-synaptic dopamine D1, D2, D3, D4 receptors in the brain+++
FluphenazineBlocks post-synaptic dopamine D1 and D2 receptors in the brain+
Atypical APs
ClozapineBlocks dopamine D2 and 5HT serotonin receptors in the brain+++
OlanzapineBlocks dopamine D1, D2, D3, D4 receptors, and serotonin 5HT2A, 5HT2C, 5HT3 and 5HT6, the alpha-1 adrenergic receptor+++
QuetiapineBlocks dopamine D2 and serotonin 5HT2A receptors+++
ZiprasidoneBlocks dopamine D2 and serotonin 5HT2A receptors-/+
RisperidoneBlocks dopamine D2 and serotonin 5HT2A receptors++
AripiprazolePartially agonizes dopamine D2, 5-HT1A receptors, blocks serotonin 5HT2A receptors+
PaliperidoneBlocks dopamine D2 and serotonin 5HT2A receptors+
ZotepineBlocks dopamine D1, D2 and serotonin 5HT2A, 5HT2C, 5HT6 receptors+++
SertindoleBlocks dopamine D2 and serotonin 5HT2A, 5HT2C alpha-1 adrenergic receptor+
AmisulprideBlocks dopamine D2 and D3 receptors+
Antidepressants
SSRIs
SertralineIncrease serotonin 5HT level by blocking reuptake at presynaptic terminals++
Fluoxetine
Excitalopram
Trazodone
Citalopram
Paroxetine
SNRIs
DuloxetineBlock serotonin and norepinephrine reuptake in the synapse, increase postsynaptic receptors’ stimulation++
Venlafaxine
Levomilnacipran
Atypical ADs
BupropionInhibits reuptake of dopamine and norepinephrine at the presynaptic cleft by binding to norepinephrine transporter and dopamine transporter+
MirtazapineIncreases release of norepinephrine into the synapse by blocking alpha-2 adrenergic receptors. Also antagonizes 5-HT receptor, increasing norepinephrine and dopamine++
ViladozoneEnhances the release of serotonin across the brain’s serotonergic pathways specifically by inhibiting the serotonin transporter
Tricyclic ADs
ImipramineIncrease norepinephrine and serotonin concentration by inhibiting reuptake at the presynaptic neuronal membrane+++
Nortriptyline
Amitriptyline
Doxepin
MAOIs
PhenelzineIncrease the levels of norepinephrine, epinephrine, serotonin, and dopamine by blocking reuptake of catecholamines and serotonin at the presynaptic neuronal membrane++
Isocarboxazie
Tranylcypromine
Table 2 Effect of psychotropic medications on the markers of de novo lipogenesis, gluconeogenesis and metabolic abnormalities in patients with psychiatric disorders
Parameters
Antipsychotic drugs
Antidepressants
De novo lipogenesis (markers)
SFAsIncreased[36,39]Increased[58,61]
MUFAsIncreased[36,39]Increased[58,61]
PUFAs1Increased[36,39]Increased[58,61]
Gluconeogenesis (precursors)
LactateIncreased[125,126]Decreased[128]
CitrateIncreased[129]?
PyruvateIncreased[129]Increased[128]
GlutamateIncreased[129,130]Increased[128]
Metabolic abnormalities
Blood glucoseIncreased[72,121]Increased[122,131]
IR/insulin level2Increased[55,133]Increased[65,74,75]
TriglyceridesIncreased[8,55,56,72]Increased[122]
Obesity (BMI)Increased[8,55,72]Increased[31,32,122]
LeptinIncreased[57,87]Increased[132]
AdiponectinIncreased[55,89]No change[65,134]
ResistinIncreased[55,89]Reduced[134]
DiabetesIncreased[8,55,72]Increased[5,65,74,135]
NAFLDIncreased[7,97,123]Increase[95,96]
Table 3 Effect of selective adjunctive/anti-inflammatory drugs on symptoms of psychosis, depression, insulin resistance and non-alcoholic fatty liver disease
Agents/drugs
Psychosis1
Depression2
Insulin resistance3
NAFLD4
AspirinReduced[136,137]Reduced[142]Reduced[151]Reduced[160]
N-acetylcysteineReduced[136,137]Reduced[143]Reduced[152]Reduced[161]
MinocyclineReduced[136,137]No change[144]Reduced[153]Increased[162]
PregnenoloneReduced[137]Reduced[145]?Reduced[163]
EstrogensReduced[136,137]Reduced[146]Reduced[154]Reduced[164]
RaloxifeneReduced[137]?May reduce[155]Reduced[165]
CurcuminReduced[138]Reduced[147]Reduced[156]Reduced[166]
PioglitazoneReduced[139]Reduced[148]Reduced[157]Reduced[167]
CelecoxibReduced[140]Reduced[149]Reduced[158]Reduced[168]
w3-PUFAsReduced[141]Reduced[150]Reduced[159]Reduced[169]