Grieving the death of a loved one is a deeply human and almost universal experience. Yet everyone grieves in their own way: while some people show hardly any visible change, others go through distress so intense that it seriously affects their daily life (Zisook and DeVaul, 1985). Some losses, such as perinatal grief, also have distinctive features of their own.
What is prolonged grief?
Prolonged grief, also known as persistent complex bereavement disorder or complicated grief, refers to an emotional pain response that remains intense for several months after a death. Losses of this kind can also worsen pre-existing conditions such as anxiety, post-traumatic stress or depression, increasing psychological distress and making emotional recovery harder.
Diagnosis and symptoms of prolonged grief
According to the latest edition of the International Classification of Diseases (ICD-11) (WHO, 2018), a diagnosis of prolonged grief requires the person to experience persistent longing for, or preoccupation with, the deceased for at least six months after the loss, together with at least one additional symptom such as sadness, guilt, anger, difficulty accepting the death, social withdrawal or impaired functioning.
The Diagnostic and Statistical Manual of Mental Disorders (DSM-5-TR) (APA, 2022) also recognises prolonged grief disorder, including persistent longing for or preoccupation with the deceased plus at least three additional symptoms. However, for the diagnosis to be made, twelve months must have passed since the loss.
Finally, in recent years researchers have begun to consider pre-death grief (Wangliu and Che, 2025). It involves a set of symptoms similar to those described above, with the particularity that it can appear several months before the loved one dies, especially in people caring for a family member through a terminal illness.
This lack of academic consensus on diagnostic criteria reflects an unmet need for social and therapeutic support in an increasingly individualistic society, which has lost the cultural customs that used to sustain grieving within families and communities (Mills et al., 2024).
Conventional treatments for prolonged grief: are they enough?
Pharmacological treatment for prolonged grief
To date, there is no solid evidence supporting the use of any medication as a stand-alone treatment for prolonged grief (Simon and Shear, 2024). However, an increase in antidepressant prescriptions has been reported after the loss of a loved one, especially during the first months of bereavement (Ornstein et al., 2020). This highlights the urgent need to develop new therapeutic interventions that truly address the core of suffering in grief, without the side effects of long-term pharmacotherapy.
Psychotherapy for prolonged grief
Psychological therapy for prolonged grief focuses both on fostering acceptance of the loss and on helping the bereaved person rebuild their life. The approach with the strongest scientific evidence, and the most effective to date, is cognitive behavioural therapy. However, its effectiveness is moderate and tends to decrease when the intervention takes place within the first six months after the loss (Komischke-Konnerup et al., 2024). This limitation leaves many bereaved people without support during the first months after the death of their loved one, precisely when the pain is most acute and intense.
New therapeutic approaches: psychedelic-assisted therapy for prolonged grief
In recent years, interest in understanding and supporting the processes surrounding the end of life and grief has grown considerably, and they are being approached from different perspectives.
In this context, psychedelic-assisted therapy has begun to stand out as an innovative and promising tool, especially for preventing and treating prolonged grief (Ehrenkranz et al., 2024). Therapy assisted with ketamine (Gowda et al., 2016), ayahuasca (Gonzalez et al., 2020) or psilocybin (Morton, 2023) for prolonged grief has not only shown significant antidepressant pharmacological effects, but also induces altered states of consciousness that can facilitate deeply transformative experiences. Many people report experiences of reunion or connection with the deceased, which open an opportunity to resolve unfinished business and to continue the bond. Others describe rebuilding their bond with their loved one, supported by feelings of compassion and forgiveness that emerge naturally during the psychedelic experience (González et al., 2019). In addition, at the neurobiological level, the neuroplasticity and neurogenesis induced by these substances translate into greater cognitive flexibility, which makes meaningful change easier throughout the therapeutic process and personal growth.
Our model of support for prolonged grief
At Clínica Synaptica, we understand that prolonged grief can become a deeply painful process that is hard to go through. Although research on psychedelics such as MDMA, psilocybin or ayahuasca for prolonged grief is ongoing, these compounds are not yet regulated by the European Medicines Agency (EMA).
At present, the only psychedelic-based treatment approved for medical use is esketamine (Spravato), a ketamine derivative, specifically indicated for treatment-resistant depression. However, the European regulatory framework allows medicines to be used off-label, that is, outside their official indication, for health conditions without specific approved treatments or when existing treatments have not proved effective.
In many cases, prolonged grief does not respond to conventional antidepressants, and it is estimated that only 50% of patients manage to adapt through cognitive behavioural therapy specialised in grief (Simon & Shear, 2024). That is why at Clínica Synaptica we offer ketamine-assisted therapy as a therapeutic alternative for people who, having tried other therapeutic approaches, still experience persistent pain over the loss of a loved one.
Our model of care combines individual ketamine-assisted therapy with a psychotherapeutic approach focused on rebuilding personal meaning. We complement the process with group support sessions designed to explore the existential dimension of grief, encouraging personal and spiritual growth in a community setting.
References
- American Psychiatric Association. (2022). Diagnostic and statistical manual of mental disorders: DSM-5-TR. Arlington, VA: American Psychiatric Publishing.
- Ehrenkranz, R., Agrawal, M., Penberthy, J. K., & Yaden, D. B. (2024). Narrative review of the potential for psychedelics to treat Prolonged Grief Disorder. International Review of Psychiatry, 1–12.
- González, D., Cantillo, J., Pérez, I., Farré, M., Feilding, A., Obiols, J. E., & Bouso, J. C. (2020). Therapeutic potential of ayahuasca in grief: A prospective, observational study. Psychopharmacology, 237, 1171–1182.
- González, D., Carvalho, M., Cantillo, J., Aixalá, M., & Farré, M. (2019). Potential use of ayahuasca in grief therapy. OMEGA—Journal of Death and Dying, 79(3), 260–285.
- Gowda, M. R., Srinivasa, P., Kumbar, P. S., Ramalingaiah, V. H., Muthyalappa, C., & Durgoji, S. (2016). Rapid resolution of grief with IV infusion of ketamine: A unique phenomenological experience. Indian Journal of Psychological Medicine, 38(1), 62–64.
- Komischke-Konnerup, K. B., Zachariae, R., Boelen, P. A., Marello, M. M., & O’Connor, M. (2024). Grief-focused cognitive behavioral therapies for prolonged grief symptoms: A systematic review and meta-analysis. Journal of Consulting and Clinical Psychology, 92(3), 236–248. https://psycnet.apa.org/doiLanding?doi=10.1037%2Fccp0000834
- Mills, J., Abel, J., Kellehear, A., Noonan, K., Bollig, G., Grindrod, A., … & Haberecht, J. (2024). The role and contribution of compassionate communities. The Lancet, 404(10448), 104–106.
- Morton, N. N. (2023). A phenomenological investigation of psilocybin use among the bereaved (Doctoral dissertation, Alliant International University).
- Ornstein, K. A. et al. (2020) New antidepressant utilization pre- and post-bereavement: a population-based study of partners and adult children. Soc. Psychiatry Psychiatr. Epidemiol. 55, 1261–1271. https://link.springer.com/article/10.1007/s00127-020-01857-1
- Simon, N. M., & Shear, M. K. (2024). Prolonged grief disorder. New England Journal of Medicine, 391(13), 1227–1236.
- Wangliu, Y. Q., & Che, R. P. (2025). A systematic review of coping and pre-death grief among dementia family caregivers. Palliative & Supportive Care, 23, e86.
- World Health Organization. (2018). ICD-11 for mortality and morbidity statistics (11th ed.). Prolonged grief disorder. https://icd.who.int/en/
- Zisook, S., & DeVaul, R. (1985). Unresolved grief. American Journal of Psychoanalysis, 45(4), 370. https://link.springer.com/article/10.1007/BF01252871
