It’s estimated that 10 to 47% of adults with a analysis of schizophrenia additionally expertise ADHD signs (Arican et al., 2018), and youngsters with ADHD have an elevated threat of growing schizophrenia later in life (Dalsgaard et al., 2020). Folks with a twin analysis of schizophrenia spectrum dysfunction (SSD) and ADHD usually tend to have difficulties in schooling and at work (Levy et al., 2015) and expertise extra extreme signs, poorer cognitive operate and elevated social difficulties. Regardless of this, there’s a lack of analysis on the expertise of people with SSD who even have ADHD signs.
ADHD and schizophrenia can have overlapping signs similar to difficulties with consideration, planning, studying and restlessness or impulsive behaviour. This will make it more durable for clinicians to obviously distinguish the 2 situations and make correct diagnoses. Misdiagnosis between ADHD and schizophrenia spectrum issues (SSD) and under-diagnosis of the twin situations is a major concern.
Whereas ADHD drugs similar to psychostimulants are related to decreased mortality (Vasiliadis et al., 2024), the image is much less clear for folks with SSD and ADHD. Many clinicians are cautious about prescribing psychostimulants due to issues they might worsen psychotic signs in some folks.
To handle this concern, Luykx et al. (2025) used information from a number of Swedish well being and inhabitants registers to check whether or not ADHD treatment use in people with schizophrenia improved or worsened their well being outcomes over 9 years.
Clinicians are cautious in prescribing ADHD treatment in folks with psychotic issues, however is that backed up by proof of threat?
Strategies
Analysis design
The authors analysed information of 9,416 folks with SSD who used ADHD treatment. SSD included diagnoses of schizophrenia, schizotypal dysfunction, delusional issues, temporary psychotic dysfunction, shared psychotic dysfunction, schizoaffective dysfunction and unspecified psychosis in response to ICD-10. ADHD drugs studied included methylphenidate, amphetamine, dexamphetamine, lisdexamphetamine, atomoxetine and modafinil.
They examined whether or not people who used ADHD treatment had decreased hospitalisation or mortality charges and appeared in additional element at particular hospitalisations similar to for psychosis, somatic situations (e.g. pneumonia or epilepsy) or cardiovascular sickness.
Statistical strategies
Analyses have been performed utilizing a within-individual design with Cox regression fashions evaluating durations of ADHD treatment use versus non-use inside the similar particular person for all outcomes. Analyses have been adjusted for time since cohort entry, temporal order of ADHD drugs, and concomitant use of psychotropic medication (antipsychotics, antidepressants, benzodiazepines, temper stabilisers, medication for addictive issues).
In addition they used between-individual Cox fashions evaluating folks utilizing ADHD treatment to these not utilizing treatment, adjusted for age, intercourse, incapacity pension, variety of earlier hospitalisations for psychosis, analysis of ADHD, substance use dysfunction, earlier suicide makes an attempt and former clozapine use.
They in contrast whether or not antipsychotic use throughout ADHD treatment elevated or decreased threat of hospitalisation and in addition studied dosages of the 2 most used ADHD drugs (methylphenidate and lisdexamphetamine) and their results on outcomes.
The research in contrast durations of ADHD treatment use and non-use inside and between folks with SSD – and assessed dangers of hospitalisation and mortality, after controlling for plenty of demographic variables.
Outcomes
All-cause hospitalisation/mortality
Over the 9 years, lisdexamphetamine was related to decreased threat of being admitted to hospital (for any purpose) or loss of life (from any trigger) whereas high-dose methylphenidate was related to a slight elevated threat particularly in these not taking antipsychotics. Average-dose methylphenidate was related to a decreased threat.
Hospitalisation for psychosis and somatic situations
Atomoxetine was related to decreased threat for psychosis-related hospitalisation. Lisdexamphetamine and moderate-dose methylphenidate was related to decreased threat for hospitalisation for psychosis whereas ADHD polytherapy elevated threat of somatic hospitalisation.
Hospitalisation for heart problems
The research discovered no vital associations between any ADHD treatment publicity and cardiovascular hospitalisation.
Dosage issues
The general sample urged that, normally, reasonable dosages of lisdexamphetamine and methylphenidate are typically safer to make use of in SSDs. Quite the opposite, very excessive dosages of methylphenidate (over 95mg/day) carried an elevated threat for hospitalisation and mortality, however this was not matched for lisdexamfetamine.
This analysis means that ADHD treatment (particularly lisdexamphetamine (at any dose) and low to medium doses of long-acting methylphenidate) could also be safer for folks with schizophrenia than many individuals assume.
Conclusion
- Lisdexamphetamine persistently confirmed protecting results throughout doses, exhibiting the strongest proof for long-term security in people with SSDs.
- Atomoxetine additionally confirmed profit.
- Methylphenidate had a U-shaped threat sample:
- Average doses have been helpful
- Very excessive doses (≥95 mg/day) have been related to elevated threat.
- There was no vital impact for most of the ADHD drugs.
The research provides reassuring findings, particularly for lisdexamphetamine in sufferers with SSD, however it doesn’t verify long-term security for all ADHD drugs. Solely lisdexamphetamine use was related to a decreased threat of each all-cause hopitalisation/mortality and somatic hopitalisations. Some drugs present potential threat similar to high-dose methylphenidate and ADHD treatment polytherapy i.e. taking greater than 1 ADHD treatment.
As there was no vital impact for most of the ADHD drugs, we don’t have sufficient proof to say if the drugs improve or lower the danger of hospitalisation.
In folks with SSDs taking ADHD treatment – lisdexamfetamine confirmed the very best security profile – whereas methylphenidate seems to warrant warning at excessive doses.
Strengths and limitations
The research’s long-term follow-up interval and huge whole pattern dimension are key strengths; nonetheless it’s unclear whether or not the subset pattern sizes for every ADHD treatment are giant sufficient to be a high-powered research, notably because it analyses retrospective information alone.
The research’s definiton of “SSDs” is expansive, together with a wide range of situations with some psychotic options – nonetheless this could threat obscuring confounding components on this research which may be specific to a dysfunction e.g. schizoaffective dysfunction, the place pervasive temper modifications and in addition antidepressant drugs might individually have an effect on hospitalisations and mortality dangers. Additional, the research statistically adjusts for plenty of demographic options and in addition different pharmacological interventions similar to earlier clozapine use, it doesn’t explicitly analyse the consequences of such changes being made – these could have unknown confounding modulating results on the suitability or efficacy of ADHD treatment in SSDs, past what could be gleaned from the paper.
One other limitation is the broad categorisation of security outcomes (e.g., “hospitalisation for psychosis”). The research didn’t discover the impact of ADHD treatment on particular SSD-related signs such because the severity of psychotic signs, specific discrepancies in constructive/destructive signs, useful impairments, or high quality of life.
The geographical confinement of this research to Swedish well being techniques might additional be a limitation to generalisability of outcomes.
Therefore, though the authors report that they discovered no proof of elevated threat of antagonistic outcomes for ADHD drugs in people with a situation underneath the schizophrenia spectrum issues (SSDs), particularly when used with antipsychotics; these findings must be interpreted as broadly reassuring, slightly than conclusive. Additional research that are prospectively designed and higher powered to evaluate every ADHD treatment individually, will probably be helpful to kind conclusions on their long-term security.
The outcomes provide pragmatic reassurance – it is a strong proof-of-concept for additional analysis, prospectively evaluating particular person ADHD drugs in folks with particular person SSDs.
Implications for follow
This analysis means that use of the ADHD drugs lisdexamphetamine, and long-acting methylphenidate at low to medium doses, seems safer than beforehand assumed in people with SSDs. Nevertheless, the authors advise warning with methylphenidate: it ought to typically be averted in sufferers with SSDs who are usually not utilizing an antipsychotic, and high-dose methylphenidate (≥95 mg each day) must be averted in all sufferers with SSDs.
For the opposite ADHD drugs examined, amphetamine, dexamphetamine, atomoxetine and modafinil, the research offers inadequate proof to attract agency conclusions about long-term security.
Given the shortage of clear threat information for a lot of drugs, the advantages of successfully treating comorbid ADHD must be fastidiously weighed in opposition to potential dangers. Therapy choices must be made utilizing a personalised, shared decision-making strategy, bearing in mind the person’s psychiatric historical past, present drugs, and threat components, with the goal of enhancing restoration and useful outcomes.
There may be a coverage influence to this paper – as the availability of lisdexamfetamine in different jurisdictions, specifically Anglophone nations, could be restricted by follow pointers that record it as a second-line treatment for ADHD. Offering its comparable security throughout doses, relative to methylphenidate that is commonly prescribed as a ‘first-line’ treatment, information from this research must be used to contemplate whether or not guideline and coverage reform is warranted, at the very least in instances the place an individual needing ADHD treatment additionally experiences an SSD.
Rising proof of security of ADHD drugs in SSDs, particularly lisdexamfetamine which is much less favoured in some nations – ought to inform not solely particular person medical follow but in addition reform in prescribing pointers and coverage.
Assertion of pursuits
None to declare.
References
Major paper
Luykx, J.J., Corbeil, O., Kärkkäinen, O. et al. Long run security of ADHD treatment in sufferers with schizophrenia spectrum issues. Mol Psychiatry 30, 4859–4867 (2025). https://doi.org/10.1038/s41380-025-03080-3
Different references
Arican, I., Bass, N., Neelam, Okay., Wolfe, Okay., McQuillin, A., Giaroli, G., & others. (2019).
Prevalence of consideration deficit hyperactivity dysfunction signs in sufferers with schizophrenia. Acta Psychiatrica Scandinavica, 139(1), 89–96. https://doi.org/10.1111/acps.12948
Dalsgaard, S., Mortensen, P. B., Frydenberg, M., Maibing, C. M., Nordentoft, M., & Thomsen, P. H. (2020). Affiliation between attention-deficit hyperactivity dysfunction in childhood and schizophrenia later in maturity. European Psychiatry, 29(4), 259–263. https://doi.org/10.1016/j.eurpsy.2013.06.004
Gough, A., & Morrison, J. (2016). Managing the comorbidity of schizophrenia and ADHD. Journal of Psychiatry & Neuroscience, 41(5), E79–E80. https://doi.org/10.1503/jpn.150251
Levy E, Traicu A, Iyer S, Malla A, Joober R. Psychotic issues comorbid with attention-deficit hyperactivity dysfunction: an essential information hole. Can J Psychiatry. 2015 Mar;60(3 Suppl 2):S48-52. PMID: 25886680; PMCID: PMC4418622.
Vasiliadis HM, Lunghi C, Rahme E, Rochette L, Gignac M, Massamba V, Diallo FB, Fansi A, Cortese S, Lesage A. ADHD drugs use and threat of mortality and unintentional accidents: a population-based cohort research. Transl Psychiatry. 2024 Feb 28;14(1):128. doi: 10.1038/s41398-024-02825-y. PMID: 38418443; PMCID: PMC10901868.
