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Current and Future Therapies for Psoriasis with a Focus on Serotonergic Drugs

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Abstract

Psoriasis is a chronic immune-mediated skin disease, with a pathogenesis resulting from a combination of genetic and environmental factors. The pathogenesis of psoriasis is driven by the interaction between innate and adaptive immune cells and keratinocytes, in a complex process mediated by cytokines and other signaling molecules. This leads to an inflammatory process with increased proliferation of epidermal cells, neo-angiogenesis, and infiltration of white cells in the skin, which cause the characteristic psoriasis plaques. Several studies have suggested that the neurotransmitter serotonin, a key mediator between the skin and the neuroendocrine system, also plays an important role in the pathogenesis of psoriasis. Psoriasis often needs long-term treatment, which can be a burden. Thus, the choice of the treatment is crucial to increase the patients’ adherence and quality of life. This review addresses the currently available systemic and topical treatments for psoriasis, used by themselves or combined with phototherapy. It particularly focuses on the importance of advanced drug delivery systems as a way to increase the drug penetration and retention in the skin, while also enhancing its solubility and stability. Finally, we discuss the role of the serotonin system in psoriasis, and summarize what is known about the effects of antidepressants, in particular specific serotonin reuptake inhibitors, on the physical symptoms of this disease.

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Abbreviations

ACT:

Acitretin

APM:

Apremilast

ASOs:

Antisense oligonucleotides

BD:

Betamethasone dipropionate

CAP:

Capsaicin

CB:

Clobetasol propionate

CLSM:

Confocal laser scanning microscopy

DDSs:

Drug delivery systems

DIT:

Dithranol

EGF:

Epidermal growth factor

EGFR:

Epidermal growth factor receptor

FDA:

Food and Drug Administration

GCs:

Glucocorticoids

HA:

Hyaluronic acid

5-HT:

Serotonin (5-hydroxytryptamine)

5-HTR:

Serotonin receptor

5-HTT:

Serotonin transport protein (SERT)

IFN-γ:

Interferon γ

IL:

Interleukin

IMQ:

Imiquimod

LCs:

Langerhans cells

LED:

Light-emitting diodes

LLL:

Low level light/laser

MAB:

Monoclonal antibody

MAO:

Monoamine oxidase

MAOI:

Monoamine oxidase inhibitor

MEs:

Microemulsions

MF:

Mometasone furoate

miRNAs:

MicroRNAs

8-MOP:

8-Methoxypsoralen

MPEG-hexPLA:

Methoxy-PEG-poly (hexylsubstituted lactide)

MTX:

Methotrexate

NEs:

Nanoemulsions

NLCs:

Nanostructured lipid carriers

OTC:

Over-the-counter

O/W:

Oil-in-water

PASI:

Psoriasis Area and Severity Index

PCL:

Poly(-caprolactone)

PDL:

Pulsed dye laser

PEG:

Polyethylene glycol

PLGA:

Poly(d,l-lactic-co-glycolic acid)

PTX:

Pentoxifylline

PUVA:

Psoralen UVA

SC:

(Skin) stratum corneum

siRNAs:

Small interfering RNAs

SLNs:

Solid lipid nanoparticles

SNRIs:

Serotonin–norepinephrine reuptake inhibitors

SSRIs:

Serotonin reuptake inhibitors

TAC:

Tacrolimus

Th:

Helper T cell

TNF-α:

Tumor necrosis factor α

W/O:

Water-in-oil

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Acknowledgments

This research was funded by Fundação para a Ciência e a Tecnologia, Portugal (UID/DTP/04138/2019 and PTDC/MEC-DER/30198/2017). The authors would like to thank Inês Marques Ribeiro for the design of the skin background in Fig. 3.

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  1. Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmácia da Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003, Lisbon, Portugal

    Ana M. Martins, Andreia Ascenso, Helena Margarida Ribeiro & Joana Marto

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Martins, A.M., Ascenso, A., Ribeiro, H.M. et al. Current and Future Therapies for Psoriasis with a Focus on Serotonergic Drugs. Mol Neurobiol 57, 2391–2419 (2020). https://doi.org/10.1007/s12035-020-01889-3

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  • DOI: https://doi.org/10.1007/s12035-020-01889-3

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