Strategies to counter antipsychotic-associated weight gain in patients with schizophrenia

Marteene, Wade; Winckel, Karl; Hollingworth, Samantha; Kisely, Steve; Gallagher, Erin; Hahn, Margaret; Ebdrup, Bjørn H; Firth, Joseph; Siskind, Dan

doi:10.1080/14740338.2019.1674809

Cited by 43 publications

(48 citation statements)

References 133 publications

(185 reference statements)

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“…For haloperidol, the ANOVA indicated a significant effect of dose [F (2,27) Figure 2B). In contrast, the high dose of haloperidol was associated with a trend for increased norepinephrine levels compared to controls at 30 mins after treatment (p = 0.06), and then significantly higher between 60 and 120 mins (p < 0.05), but no longer at 180 mins (p = 0.07).…”

Section: Norepinephrinementioning

confidence: 99%

“…With clozapine, the ANOVA indicated a significant effect of dose [F (2,27 Post-hoc analysis demonstrated that levels of norepinephrine with the low dose of clozapine did not differ at any time point from controls ( Figure 2C). However, the high dose of clozapine evinced a large, highly significant increase in norepinephrine levels compared to both the controls and the low dose of clozapine at all time points after treatment (p < 0.001).…”

Section: Norepinephrinementioning

confidence: 99%

“…For clozapine, ANOVA indicated a significant effect of dose [F (2,27) = 14.15, p < 0.001], time [F (4,108) = 8.14, p < 0.001] and a dose × time interaction [F (8,108) = 5.27, p < 0.001]. The posthoc analysis confirmed that showed that the low dose of clozapine and controls did not differ at any time point in epinephrine levels (Figure 3C), but the high dose of clozapine had higher epinephrine levels than both other groups at all time points after drug treatment (p < 0.01).…”

Section: Norepinephrinementioning

confidence: 99%

“…With olanzapine, the analysis showed significant main effects of dose [F (2,27) Follow-up post-hoc tests revealed that both doses of olanzapine caused a significant increase in epinephrine levels by 30 mins compared to controls (p ≤ 0.01) ( Figure 3D), but by 60 mins the lower dose of olanzapine did not differ from controls, for the duration of the test. Epinephrine levels with the higher dose of olanzapine remained significantly higher than both other groups from 60 through to 180 mins (p < 0.005).…”

Section: Norepinephrinementioning

confidence: 99%

“…As it is likely that invasive procedures will be required to fully elucidate the biochemical pathways involved, which may not be appropriate for application in humans, there is a key need to develop translational animal models of these drug side-effects. The use of preclinical paradigms offers the additional benefit of helping to disentangle the multifactorial causes of metabolic dysregulation in psychiatric illness, where variables such as diet, exercise, and drug use can all contribute to cardiometabolic dysregulation (25)(26)(27). Fortunately, the past 10-15 years has seen significant advances in animal models of the metabolic side-effects of antipsychotic drugs (28), which have demonstrated that many of these compounds cause acute glucose dysregulation and insulin resistance independent of weight gain (29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39).…”

Section: Introductionmentioning

confidence: 99%

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Differential Effects of Acute Treatment With Antipsychotic Drugs on Peripheral Catecholamines

Boyda

Tse

et al. 2020

Front. Psychiatry

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Antipsychotic drugs represent the most effective treatment for chronic psychotic disorders. The newer second generation drugs offer the advantage of fewer neurological side-effects compared to prior drugs, but many cause serious metabolic side-effects. The underlying physiology of these side-effects is not well-understood, but evidence exists to indicate that the sympathetic nervous system may play an important role. In order to examine this possibility further, we treated separate groups of adult female rats acutely with either the first generation antipsychotic drug haloperidol (0.1 or 1 mg/kg) or the second generation drugs risperidone (0.25 or 2.5 mg/kg), clozapine (2 or 20 mg/kg), olanzapine (3 or 15 mg/kg) or vehicle by intraperitoneal injection. Blood samples were collected prior to drug and then 30, 60, 120, and 180 mins after treatment. Plasma samples were assayed by HPLC-ED for levels of norepinephrine, epinephrine, and dopamine. Results confirmed that all antipsychotics increased peripheral catecholamines, although this was drug and dose dependent. For norepinephrine, haloperidol caused the smallest maximum increase (+158%], followed by risperidone (+793%), olanzapine (+952%) and clozapine (+1,684%). A similar pattern was observed for increases in epinephrine levels by haloperidol (+143%], olanzapine (+529%), risperidone (+617%) then clozapine (+806%). Dopamine levels increased moderately with olanzapine [+174%], risperidone [+271%], and clozapine [+430%]. Interestingly, levels of the catecholamines did not correlate strongly with each other prior to treatment at baseline, but were increasingly correlated after treatment as time proceeded. The results demonstrate antipsychotics can potently regulate peripheral catecholamines, in a manner consistent with their metabolic liability.

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Section: Norepinephrinementioning

confidence: 99%

Section: Norepinephrinementioning

confidence: 99%

Section: Norepinephrinementioning

confidence: 99%

Section: Norepinephrinementioning

confidence: 99%