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Dermatology

Cite as: Archiv EuroMedica. 2026. 16; 4. DOI 10.35630/2026/16/Iss.4.28

Received 14 July 2026;
Accepted 17 August 2026;
Published 19 August 2026

EFFECTS OF ISOTRETINOIN ON PSYCHOLOGICAL WELL-BEING AND MENTAL HEALTH: A NARRATIVE REVIEW

Ewa Dapkiewicz¹ , Sylwia Haba² ,
Dawid Gąsowski³ , Izabela Grzyb⁴ ,
Jan Szewczyk⁴ , Alicja Smolińska⁴ ,
Maria Bołoz⁵ , Zuzanna Wątek⁵ ,
Katarzyna Łysynkiewicz⁵ , Patrycja Krawczyk⁶

¹ Independent Public Health Care Facilities of the Ministry of Interior and Administration in Białystok, Poland
² University Clinical Hospital of Białystok, Podlasie, Poland
³ Independent Public Health Care Facility in Łapy, Poland
⁴ Polish Red Cross Maritime Hospital: Gdynia, Poland
⁵ Jędrzej Śniadecki Regional Hospital, Białystok, Poland
⁶ The Primary Regional Hospital in Kielce, Poland

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ABSTRACT

Background

Isotretinoin is an effective treatment for severe and treatment-resistant acne vulgaris, but concerns persist regarding possible psychiatric adverse effects, including depression, anxiety, suicidal behaviour, and other psychiatric manifestations. Interpretation of these outcomes is complicated by the substantial psychological burden of acne itself and by changes in quality of life during successful treatment.

Aim

To evaluate current evidence regarding the association between isotretinoin therapy and mental health outcomes, with particular attention to potential neurobiological mechanisms, clinical and epidemiological findings, and the psychological burden of acne.

Materials and Methods

A narrative review was conducted using PubMed/MEDLINE and Google Scholar. English-language publications from 1982 to 2026 were considered, with priority given to more recent clinical and epidemiological evidence. Eligible sources included clinical and observational studies, cohort studies, case reports and case series, experimental and preclinical studies, systematic reviews, meta-analyses, clinical guidelines, consensus statements, and narrative reviews. Of 87 potentially relevant publications identified, 61 were included in the final narrative synthesis.

Results

Experimental and neurobiological studies suggest biologically plausible mechanisms related to retinoid signalling, serotonergic neurotransmission, hippocampal neurogenesis, and brain regions that regulate emotional processes. However, large observational studies and meta-analyses have generally not demonstrated an increased population-level risk of depression, anxiety, suicidal behaviour, or other psychiatric disorders among isotretinoin users. Rare individual psychiatric reactions have been reported, particularly in patients with pre-existing psychiatric vulnerability. Acne itself is associated with depression, anxiety, reduced self-esteem, impaired quality of life, and suicidal ideation, while successful treatment may be accompanied by improvements in psychological well-being.

Conclusions

Current evidence does not support a definitive causal relationship between isotretinoin therapy and psychiatric disorders. Mental health outcomes should be interpreted in the context of baseline psychiatric status, acne severity, treatment response, and changes in quality of life. Baseline mental health assessment and regular monitoring during isotretinoin therapy remain advisable.

Keywords: isotretinoin, acne vulgaris, mental health, psychiatric effects, depression, anxiety, quality of life.

1. INTRODUCTION

Isotretinoin (13-cis-retinoic acid) is an oral retinoid and vitamin A derivative widely regarded as the most effective treatment for severe and treatment-resistant acne vulgaris. Since its introduction into clinical practice, it has remained a cornerstone of dermatological therapy due to its ability to target multiple pathogenic mechanisms of acne [1-3]. Isotretinoin reduces sebaceous gland size and activity, normalizes follicular keratinization, inhibits the proliferation of Cutibacterium acnes, and exerts anti-inflammatory and immunomodulatory effects [1, 3, 4].

Despite its well-established efficacy, concerns have been raised regarding potential psychiatric adverse effects associated with isotretinoin therapy. Numerous studies have investigated a possible relationship between isotretinoin use and the occurrence of depression, anxiety, mood disturbances, and suicidal behaviour. However, the available evidence remains inconsistent, and a definitive causal association has not been established.

Several biological mechanisms have been proposed to explain the potential effects of isotretinoin on mental health. Retinoic acid receptors are expressed in multiple brain regions involved in emotional regulation, including the hippocampus, hypothalamus, and prefrontal cortex. Experimental studies suggest that retinoids may influence neurogenesis, synaptic plasticity, and serotonergic neurotransmission. In addition, neuroimaging studies have reported alterations in brain metabolism in regions implicated in mood regulation, while metabolic changes induced by isotretinoin, such as elevated homocysteine levels and reduced vitamin B12 and folate concentrations, have also been proposed as contributing factors [3, 5-7,13].

Interpretation of psychiatric outcomes during isotretinoin therapy is complicated by the fact that acne itself is associated with considerable psychological burden. Patients with acne frequently experience reduced self-esteem, impaired quality of life, depression, anxiety, and suicidal ideation. Therefore, distinguishing between the psychological consequences of acne and the potential psychiatric effects of isotretinoin remains challenging [8,9].

2. AIMS AND OBJECTIVES

The aim of this narrative review is to evaluate current evidence regarding the association between isotretinoin therapy and mental health outcomes, with particular emphasis on depression, anxiety, suicidal behaviour, and other psychiatric manifestations.

The objectives of the review are:

1. To examine the potential neurobiological mechanisms through which isotretinoin may influence mood regulation and psychiatric outcomes.
2. To analyse the available clinical and epidemiological evidence concerning depression, anxiety, suicidal behaviour, and other psychiatric manifestations during isotretinoin therapy.
3. To assess the psychological burden of acne and changes in quality of life as factors that may influence the interpretation of mental health outcomes during isotretinoin treatment.

3. MATERIALS AND METHODS

This study was designed as a narrative review of the literature concerning the association between isotretinoin therapy and mental health outcomes. Its purpose was to integrate and critically discuss evidence on potential neurobiological mechanisms, psychiatric outcomes, and the influence of acne-related psychological burden and quality of life on the interpretation of mental health outcomes during isotretinoin therapy. The literature search was carried out using PubMed/MEDLINE and Google Scholar and included publications published from 1982 to 2026. Publications published between 2019 and 2026 were prioritised in order to reflect more recent clinical and epidemiological evidence, while older studies were included when they provided historically important, mechanistic, or clinically relevant data.

The PubMed/MEDLINE search included the following terms: “isotretinoin”, “central nervous system”, “mental health”, “psychiatric effects”, “depression”, “mood changes”, “acne”, “anxiety”, “suicidal ideation”, and “quality of life”. A simplified search strategy based on the same main terms was applied in Google Scholar.

Publications were considered eligible if they were written in English, available as full texts, and relevant to the association between isotretinoin therapy and mental health outcomes. Eligible sources included original clinical and observational studies, cohort studies, case reports and case series, experimental and preclinical studies, systematic reviews, meta-analyses, clinical guidelines, consensus statements, and narrative reviews.

Publications were excluded if they were duplicates, written in languages other than English, available only as conference abstracts, unrelated to the aims of the review, or provided insufficient clinical or methodological information for interpretation.

An initial assessment identified 87 potentially relevant publications. After evaluation of their relevance to the aims of the review and the clinical or scientific value of the reported evidence, 61 publications were included in the final narrative synthesis. The included literature was reviewed narratively and analysed qualitatively, with particular attention to study design, psychiatric outcomes, potential confounding factors, and the limitations of the available evidence.

4. RESULTS

4.1 The impact of isotretinoin on the central nervous system

Isotretinoin, a derivative of vitamin A, has been shown to exert effects on the central nervous system through retinoid signaling pathways and retinoic acid receptors (RARs). Retinoic acid, the biologically active form of vitamin A, is responsible for most of its physiological effects and regulates gene expression via binding to nuclear receptors. Increasing evidence suggests that retinoic acid signaling is also present in the adult human brain, indicating a potential sensitivity of the central nervous system to changes in RA levels. RARα receptors are expressed in the hippocampus, thalamus, and pons, whereas RARβ is found in the hypothalamus, striatum, and medulla oblongata. RARs are involved in the regulation of neuronal processes, cognitive function, mood, and stress responses [10,11].

Given the distribution of RARs in limbic structures such as the amygdala, prefrontal cortex, and hippocampus, regions critically involved in emotional regulation and the pathophysiology of depression, retinoid signaling may influence key neurotransmitter systems, including dopaminergic, serotonergic, and noradrenergic pathways. Consequently, alterations in retinoid signaling may potentially contribute to changes in behavior and affective disorders. Moreover, both excessive retinoid exposure and vitamin A deficiency may affect central nervous system function, with high levels being associated with psychiatric symptoms, while deficiency has been linked to impairments in learning and memory [11].

Experimental findings suggest that isotretinoin may alter serotonergic neurotransmission by increasing intracellular serotonin levels in raphe-derived neurons, while simultaneously upregulating presynaptic 5-HT1A receptors and the serotonin reuptake transporter (SERT), thereby reducing serotonergic firing and serotonin signaling in the brain. Such alterations have been proposed as potential mechanisms underlying depression-like behaviors observed in experimental animal models [10,42].

Isotretinoin has also been associated with alterations in homocysteine metabolism and reductions in serum vitamin B12 and folate levels. Because disturbances in these pathways have been linked to depressive symptoms and cognitive dysfunction, they have been proposed as additional mechanisms potentially contributing to psychiatric manifestations during treatment [12,13].

4.2. Psychiatric implications of acne vulgaris

Acne vulgaris is a common dermatological condition with substantial psychological implications. Because lesions frequently affect visible areas such as the face, chest, and back, the disease may negatively influence self-esteem, body image, social functioning, and overall quality of life. This is particularly relevant in patients considered for isotretinoin therapy, who often present with severe, persistent, or scarring acne, which may already be associated with psychological distress prior to treatment initiation [14,15].

The psychological impact of acne is especially pronounced in adolescents and young adults, when appearance, peer acceptance, personal perceptions of acne, and social relationships play an important role [14,16,34]. Patients have been reported to experience embarrassment, shame, reduced confidence, social withdrawal, and fear of negative evaluation. Importantly, the emotional burden does not always correlate with clinical severity, as even mild or moderate acne may lead to significant distress if the patient perceives the disease as difficult to control or socially limiting [14,16].

Several studies have reported higher rates of depressive and anxiety symptoms among individuals with acne [17,33]. A meta-analysis showed a significant association between acne vulgaris and both depression and anxiety, although the strength of this relationship may vary depending on age, sex, acne severity, study design, and the tools used to assess mental health [17]. These findings suggest that acne itself may be an important psychological burden and should be considered when evaluating psychiatric symptoms during acne treatment.

Acne has also been associated with suicidal ideation; however, the nature of this relationship remains complex and likely multifactorial. In a population-based study conducted by Halvorsen et al., adolescents with substantial acne more often reported suicidal thoughts, mental health problems, and social impairment [18]. Moreover, Xu et al. also suggested a possible association between acne and suicidal outcomes. Depression, anxiety, low self-esteem, bullying, social isolation, and previous psychiatric history were all suggested as plausible contributors to this risk [19].

4.3. Quality of life in patients with acne vulgaris and its relevance to isotretinoin treatment

Health-related outcomes extend beyond objective disease severity and include patients’ subjective well-being, daily functioning, and overall quality of life [20,21]. Acne vulgaris can substantially affect health-related quality of life, psychological well-being, self-esteem, body image, and social functioning. This is particularly relevant in patients considered for isotretinoin therapy, who often have severe or treatment-resistant acne. Importantly, the psychological burden of acne does not necessarily correlate with its objective clinical severity, and even relatively mild disease may cause considerable psychosocial distress and impaired quality of life [23,24,32].

Assessment of treatment outcomes should therefore include not only objective clinical measures, such as lesion counts and inflammatory severity, but also patient-reported outcomes. Clinical improvement may be accompanied by increased self-confidence, better social functioning, and improved psychological well-being, which are not fully captured by conventional measures of acne severity [22,23,25]. Quality-of-life assessment is therefore particularly important when interpreting changes in mental health during isotretinoin therapy.

Several validated instruments are used to assess quality of life in patients with dermatological disorders, including acne. The Dermatology Life Quality Index (DLQI) evaluates the impact of skin disease on symptoms and feelings, daily activities, interpersonal relationships, work or school, leisure activities, and treatment-related burden [22,26,27]. The Cardiff Acne Disability Index (CADI) is an acne-specific instrument that focuses on the psychosocial consequences of acne, including embarrassment, frustration, concerns about appearance, and impairment of social interactions and everyday activities [28-30].

Quality-of-life impairment is not unique to acne and has also been demonstrated in other dermatological conditions, illustrating the broader relationship between chronic skin symptoms and emotional well-being [31]. In acne, however, this aspect is particularly important in studies of isotretinoin because acne itself is an important factor that may confound the interpretation of psychiatric outcomes during isotretinoin therapy.

Improvement in skin lesions may reduce embarrassment, social withdrawal, anxiety, and depressive symptoms, whereas persistent or severe acne may contribute to psychological distress independently of pharmacological treatment [49,50]. Clinical studies evaluating isotretinoin have reported improvement in quality of life during therapy. Kaymak et al. found reductions in anxiety and depression scores together with improvements in quality of life after isotretinoin treatment, while Marron et al. also reported improvement in anxiety, depression, quality of life, and patient satisfaction [49,50]. These findings suggest that successful treatment of acne may contribute to improved psychological well-being.

Consequently, changes in mood, anxiety, or other psychological outcomes observed during isotretinoin treatment should not automatically be attributed to isotretinoin exposure. They should be considered together with baseline psychiatric status, acne severity, treatment response, and changes in quality of life. This distinction is important when evaluating the overall relationship between isotretinoin therapy and mental health.

4.4. Isotretinoin and depression

Since its introduction for the treatment of severe acne, isotretinoin has been the subject of concern regarding potential psychiatric adverse effects, including depressive symptoms. Interest in this possible association was initially prompted by evidence linking hypervitaminosis A with neuropsychiatric manifestations such as irritability, mood changes, and depressive symptoms. This led to the hypothesis that isotretinoin, as a synthetic retinoid and vitamin A derivative, might exert similar effects on mood and behavior [11,35].

Early clinical safety signals were derived primarily from case reports and small case series describing the onset of depressive symptoms during isotretinoin therapy, with improvement observed in some cases following discontinuation of the drug. The first publication raising this concern was by Meyskens Jr. in 1982 and involved oncology patients treated with isotretinoin, some of whom developed depressive symptoms and suicidal ideation during treatment [36]. One year later, Hazen et al. reported depressive symptoms in 6 of 110 patients receiving retinoids for acne or disorders of keratinization, providing early evidence that this issue might also be relevant in dermatological populations [35].

Subsequent cohort studies and meta-analyses have evaluated the association between isotretinoin use and the risk of depression. The majority of these studies have not demonstrated an increased risk of developing depression among patients treated with isotretinoin. Moreover, some studies have reported a reduction in depressive symptom severity following treatment [8,9,37,38].

Potential neurobiological mechanisms that might contribute to mood changes during isotretinoin treatment have been discussed in Section 4.1. These include effects on retinoid signaling, serotonergic neurotransmission, hippocampal neurogenesis, and brain regions involved in emotional regulation [6,7,11,39,42]. The relevance of the hippocampus to depressive disorders is supported by evidence linking depression with alterations in hippocampal function and reduced hippocampal volume [40,41]. Alterations in cortical and limbic regions involved in emotional regulation have also been implicated in mood disorders [43]. However, these findings are derived largely from experimental, animal, neuroimaging, and psychiatric studies and do not establish that isotretinoin causes depression in clinical populations.

Overall, current clinical and epidemiological evidence does not support an increased population-level risk of depression associated with isotretinoin therapy. Nevertheless, the occurrence of rare individual reactions cannot be excluded, particularly in patients with pre-existing psychiatric vulnerability.

4.5. Suicidality and severe psychiatric outcomes

Early reports of suicide and suicidal ideation among patients receiving isotretinoin emerged during the 1980s and 1990s [35]. Subsequent case reports and post-marketing surveillance data prompted regulatory agencies, including the FDA, Health Canada, and the MHRA, to issue warnings regarding potential psychiatric adverse effects and to incorporate such warnings into product labeling [12].

The interpretation of suicidal ideation and suicide attempts among isotretinoin-treated patients is complicated by the substantial psychological burden associated with acne itself. Acne has been linked to social stigma, impaired social functioning, reduced quality of life, depression, and suicidal ideation, suggesting that affected individuals may already constitute a population at increased psychiatric risk before treatment initiation [18,44,45]. Biological hypotheses have proposed that any potential association between isotretinoin and suicidal behavior may be mediated indirectly through effects on serotonergic neurotransmission, hippocampal neurogenesis, and neural pathways involved in emotional regulation [11,46,47].

In the population-based study, Sundström et al. demonstrated that the rate of suicide attempts was already elevated among patients with acne prior to the initiation of isotretinoin therapy. This increased risk remained during treatment and gradually declined following its completion. The authors suggested that severe acne itself, rather than isotretinoin exposure, was the most likely explanation for these findings [48].

Similarly, in French population-based study, Droitcourt et al. found that a history of psychiatric disorders was a stronger predictor of suicide attempts than isotretinoin exposure [37].

Furthermore, a large cohort study conducted by Kridin et al. did not identify an increased risk of suicide attempts or self-harm among patients treated with isotretinoin [38]. Comparable findings were reported by Tan et al. in a recent meta-analysis, which found no evidence of an increased risk of suicidal behaviour associated with isotretinoin use at the population level [8].

4.6. Anxiety, mood disorders, and other psychiatric manifestations

Anxiety symptoms are frequently discussed together with depression in patients treated with isotretinoin. However, their interpretation is complicated because acne itself may cause social anxiety, avoidance, embarrassment, and reduced self-confidence. In prospective studies, improvement of skin lesions has often been followed by better quality of life and lower anxiety scores, suggesting that successful acne therapy may reduce psychological distress rather than worsen it. In a study of 346 patients with moderate acne treated with oral isotretinoin, anxiety and depression scores measured with the Hospital Anxiety and Depression Scale decreased after 30 weeks, together with improvement in Dermatology Life Quality Index and SF-36 results [49,50].

At the same time, anxiety, nervousness, panic attacks, sleep disturbances, irritability, and mood swings have been reported during isotretinoin therapy. In a large analysis of psychiatric adverse events submitted to the US Food and Drug Administration from 1997 to 2017, depressive disorders were the most frequently reported category, but emotional lability and anxiety disorders were also common. Anxiety disorders accounted for 2412 reports and emotional lability for 2962 reports; insomnia and psychotic symptoms were less frequent. These data indicate that non-depressive psychiatric symptoms are clinically relevant, but spontaneous adverse-event reports cannot prove causality because they are affected by underreporting, notoriety bias, overlapping symptoms, acne severity, and pre-existing psychiatric vulnerability [51].

In a 2024 meta-analysis conducted by Tan et al., a more reassuring population-level view was provided. In pooled observational data, the 1-year absolute risk of anxiety among isotretinoin users was estimated at 6.67%, while mood disorder and bipolar disorder were less frequent with the 1-year absolute risk at 2.32% and 0.57%, respectively. Importantly, isotretinoin was not associated with a higher relative risk of anxiety, psychotic disorders, sleep disorders, depression, or all psychiatric disorders compared with non-users. These results do not exclude rare idiosyncratic reactions in individual patients, but they argue against a broad increase in psychiatric morbidity attributable to isotretinoin alone [8].

The impact of isotretinoin therapy on mood instability was also analysed by researchers. Reports of irritability, affective lability, hypomanic symptoms, manic episodes, and exacerbation of bipolar disorder have been described, mostly in case reports and small retrospective series. Patients with bipolar disorder were observed to be particularly vulnerable to mood destabilization [52,53]. Schaffer et al. reported in a retrospective chart review of bipolar patients exposed to isotretinoin that most participants experienced worsening mood symptoms and several developed suicidal ideation, with improvement after discontinuation in many cases. Although the sample was small and cannot define risk for the general acne population, it supports careful psychiatric history-taking before treatment, especially in patients with known bipolar disorder, previous manic or mixed episodes, or strong family history of mood disorders [52].

Psychotic symptoms, obsessive-compulsive symptoms, aggression, anhedonia, and panic attacks have also been described, but the evidence is mainly based on case reports, pharmacovigilance data, or regulatory safety reviews. Such reports are important because they may reveal rare adverse reactions that are not visible in cohort studies. However, they should be interpreted cautiously, as symptoms may be influenced by adolescence, acne-related distress, comorbid psychiatric disease, substance use, family history, and other medications. Regulatory agencies have therefore generally adopted a precautionary approach. For example, the 2025 Therapeutic Goods Administration safety update advised mental health assessment before initiation and monitoring for mood-related changes during treatment, while noting that a relationship between isotretinoin and psychiatric disorders could not be ruled out [54,55].

Fornaro et al. reported the case of a patient who developed obsessive-compulsive disorder at the age of 23 years during isotretinoin therapy. The patient had been receiving isotretinoin since the age of 16 years at doses ranging from 10 to 20 mg/day [56]. The occurrence of panic attacks during isotretinoin treatment has also been described in several case reports, including cases involving a 20-year-old and a 17-year-old patient [57,58].

Several case reports of psychosis associated with isotretinoin therapy have been described in the literature. These include a 20-year-old woman with no personal or family history of psychiatric disorders, a 27-year-old man who developed psychotic symptoms within a few days of initiating isotretinoin treatment, with symptom resolution following drug discontinuation, and a 25-year-old woman with a family history of bipolar disorder in a first-degree relative. In all cases, psychotic symptoms improved following discontinuation of isotretinoin and treatment with antipsychotic medications [59-61].

Overall, anxiety and other psychiatric manifestations during isotretinoin treatment should be assessed as part of a broader clinical context rather than attributed automatically to the drug. Available epidemiological evidence does not support a general increase in anxiety, psychosis, sleep disorders, or mood disorders among isotretinoin users, but individual susceptibility remains possible.

Characteristics and main findings of studies on isotretinoin and mental health effects are summarized in Table 1.

5. DISCUSSION

The available evidence suggests that the association between isotretinoin therapy and psychiatric outcomes remains complex and cannot be simply explained by a cause-and-effect mechanism. Although several biologically plausible pathways have been proposed, including alterations in serotonergic neurotransmission, hippocampal neurogenesis, and retinoid signaling within brain regions involved in emotional regulation, these findings originate mainly from experimental, animal, neuroimaging, and other neurobiological studies [3,5-7,11,39-43]. Conversely, in most large observational studies and recent meta-analyses, no increased population-level risk of depression, anxiety, or suicidal behaviour associated with isotretinoin treatment was demonstrated. Instead, several studies report improvements in psychological well-being that parallel the clinical improvement of acne [49,50].

The psychological burden associated with acne vulgaris is an important factor when interpreting psychiatric outcomes during isotretinoin therapy. Depression, anxiety, impaired quality of life, reduced self-esteem, and suicidal ideation may already be present before treatment initiation [14,16-19,33,44,45]. Consequently, psychiatric symptoms observed during treatment should be interpreted together with baseline psychiatric status, acne severity, treatment response, and changes in quality of life rather than attributed automatically to isotretinoin exposure.

The analysed studies are considerably heterogeneous with respect to study design, patient populations, psychiatric assessment tools, duration of follow-up, and control for baseline mental health status. This heterogeneity limits direct comparison of findings and may contribute to inconsistent conclusions.

Despite reassuring epidemiological evidence, individual predisposition to psychiatric adverse effects must be taken into consideration. Case reports and pharmacovigilance data describing depression, mood instability, psychosis, or exacerbation of bipolar disorder suggest that rare idiosyncratic reactions may occur, particularly in patients with pre-existing psychiatric disorders, including mood disorders [51-53,56-61]. These findings should be interpreted together with the large observational studies and meta-analyses that have not demonstrated an increased population-level psychiatric risk [8,37,38]. Therefore, current evidence supports a cautious but balanced clinical approach rather than avoidance of isotretinoin.

Routine assessment of mental health before treatment initiation and regular monitoring throughout therapy should be considered an integral component of acne management [54, 55]. Future prospective studies using standardized psychiatric outcome measures, longer follow-up periods, and careful adjustment for baseline psychological status are needed to clarify further whether specific patient subgroups may be particularly vulnerable to adverse psychiatric effects during isotretinoin treatment.

5.1. Limitations

This article is a narrative review and has several methodological limitations. The literature search was limited to PubMed/MEDLINE and Google Scholar and included only publications written in English, which may have resulted in the omission of relevant evidence available in other databases or languages. Study selection was performed narratively by the authors based on relevance to the aims of the review. In addition, no formal comparison of methodological quality was performed across the different types of included evidence.

This study is also limited by the heterogeneity of the included literature, which comprised case reports, retrospective cohort studies, meta-analyses, systematic and narrative reviews, and preclinical studies. The included studies varied substantially in study design, patient populations, settings, psychiatric outcome measures, and duration of follow-up, limiting direct comparability. Interpretation is further complicated by differences in baseline psychiatric status, acne severity, and treatment response. It should also be noted that acne vulgaris itself may substantially influence psychological well-being and therefore confound the assessment of psychiatric outcomes during isotretinoin therapy.

6. CONCLUSIONS

Current evidence does not support a definitive causal relationship between isotretinoin therapy and depression, anxiety, suicidal behaviour, or other psychiatric manifestations. Although experimental and neurobiological studies suggest biologically plausible mechanisms involving serotonergic neurotransmission, hippocampal neurogenesis, retinoid signaling, and brain regions involved in emotional regulation, these findings do not establish causality in clinical populations.

Large observational studies and meta-analyses have generally not demonstrated an increased population-level psychiatric risk among isotretinoin users, although rare individual psychiatric reactions may occur, particularly in patients with pre-existing psychiatric vulnerability.

The psychological burden of acne vulgaris and changes in quality of life are important confounding factors when interpreting mental health outcomes during treatment. Psychiatric symptoms should therefore be assessed in the context of baseline psychiatric status, acne severity, treatment response, and changes in quality of life.

Overall, baseline mental health assessment and regular monitoring during isotretinoin therapy remain advisable.

DISCLOSURE

Author Contributions

All authors contributed substantially to the conception and design of the study, literature analysis and interpretation, drafting and critical revision of the manuscript, and all authors approved the final version for publication. Conceptualization and methodology: Zuzanna Wątek, Patrycja Krawczyk, Maria Bołoz, Sylwia Haba, Katarzyna Łysynkiewicz, Jan Szewczyk. Literature review and data extraction: Zuzanna Wątek, Patrycja Krawczyk, Katarzyna Łysynkiewicz, Sylwia Haba, Izabela Grzyb. Writing - original draft: Ewa Dapkiewicz, Dawid Gąsowski, Maria Bołoz, Jan Szewczyk, Zuzanna Wątek, Alicja Smolińska, Izabela Grzyb. Writing - review and editing: Sylwia Haba, Dawid Gąsowski, Katarzyna Łysynkiewicz, Izabela Grzyb, Jan Szewczyk, Zuzanna Wątek. Supervision: Izabela Grzyb.

USE OF ARTIFICIAL INTELLIGENCE

The authors acknowledge the use of artificial intelligence tools for language editing and improvement of grammatical accuracy. All content was critically reviewed by the authors to ensure scientific accuracy and logical consistency.

FUNDING

This article received no external funding.

CONFLICT OF INTEREST

The authors declare no conflicts of interest.

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