Brain Zaps: A Case Series on Electrical Sensations Following Antidepressant Discontinuation

Narrative Abstract

Brain zaps are abrupt, shock-like sensory disturbances most often associated with antidepressant discontinuation and are a recognized feature of antidepressant discontinuation syndrome (ADS). While commonly described with older selective serotonin reuptake inhibitors (SSRIs), limited data exist regarding less commonly highlighted serotonergic agents and serotonin-norepinephrine reuptake inhibitors (SNRIs).

We present a case series of patients who reported brain zaps during dose reduction and discontinuation of less commonly highlighted serotonergic agents, with emphasis on vilazodone, an SSRI and 5-HT1A partial agonist, and duloxetine, a SNRI. The patients described their symptoms as sudden electric shock–like sensations localized to the head, sometimes accompanied by transient disequilibrium. Clinical timelines, medication exposure, and symptom resolution were reviewed.

These cases show that brain zaps may occur with newer serotonergic agents and may be underrecognized in clinical practice, underscoring the need for clinician awareness, anticipatory guidance, and careful tapering strategies.

Recognition of brain zaps across a broader range of antidepressants may improve patient counseling, reduce unnecessary diagnostic evaluations, and support safer antidepressant discontinuation in clinical practice.

Introduction. This report describes the clinical features of brain zaps associated with less commonly highlighted serotonergic agents, particularly vilazodone, an SSRI and 5-HT1A partial agonist, and duloxetine, a SNRI. 

Brain zaps are a distinctive sensory phenomenon characterized by abrupt, shock-like sensations, most often localized to the head, and are frequently reported during discontinuation of serotonergic antidepressants. These sensations, often described as “electric shocks” or “jolts,” may also be accompanied by non-electric vibratory feelings or audible zapping sounds and are increasingly recognized as a clinically relevant component of ADS.^1-5

Although brain zaps have been described most often with selective serotonin reuptake inhibitors and SNRIs, they remain underrecognized in clinical practice and are not consistently quantified in clinical trials. Discontinuation symptoms appear to be more common with abrupt cessation, rapid tapering, higher doses, and shorter half-life agents, although symptoms may still occur despite gradual dose reduction.^2-10

Published reports describing brain zaps with newer serotonergic agents remain limited. We present 2 cases of brain zaps occurring during dose reduction of vilazodone (Table 1) and duloxetine (Table 2). ^7,8,11

Table 1. Vilazodone profile

Table 2. Duloxetine profile

Case 1

Introductory sentence. A 62-year-old man with a history of recurrent major depressive disorder presented to primary care for management of depressive symptoms after discontinuing prior antidepressant therapy due to medication-associated blurred vision.

History. The patient had a history of hyperlipidemia and hypothyroidism, for which he was taking levothyroxine 112 mcg daily, and a surgical history of left total knee replacement. He presented with recurrent major depressive symptoms. His psychiatric history included prolonged treatment with citalopram, up to 40 mg daily, and sertraline, up to 150 mg daily, followed by venlafaxine, up to 225 mg daily for 9 months, due to worsening depressive symptoms. Although venlafaxine provided symptom resolution, the patient requested discontinuation due to persistent blurry vision. A cross-taper to fluoxetine, up to 30 mg daily, was implemented to facilitate gradual discontinuation, given fluoxetine’s longer half-life. Fluoxetine was subsequently tapered and discontinued without complication.

Three months after stopping medication, the patient experienced a recurrence of depressive symptoms, including anhedonia, amotivation, and feelings of worthlessness. His Patient Health Questionnaire (PHQ-9) was 21, and the Generalized Anxiety Disorder Questionnaire (GAD-7) was 14. His primary care provider initiated vilazodone 20 mg daily.

After 6 weeks, the patient reported improvement in mood and anxiety, with PHQ-9 decreasing to 13 and GAD-7 to 7. The patient was titrated to vilazodone 40 mg daily. Follow-up visits at 3 and 6 months confirmed sustained improvement, with PHQ-9 of 2 and GAD-7 of 3 at 6 months. Given his stable response and lack of side effects, including the resolution of prior blurry vision, his physician recommended continuing vilazodone.

After 1 year of treatment, the patient requested to discontinue vilazodone. His physician initiated a taper from 40 mg to 20 mg daily. Four days after the dose reduction, the patient contacted his primary care office reporting chills, fatigue, headache, and intermittent brain zaps, described as electric shock sensations that interfered with his ability to drive.

Diagnostic testing: Diagnostic evaluation was performed to assess potential medical or neurologic causes of the patient’s symptoms. The patient was evaluated in clinic, and his physical examination was unremarkable. Vital signs were within normal limits, and a neurologic examination revealed no focal deficits, abnormal coordination, or gait instability. His physician ordered laboratory testing (Table 3) to evaluate for alternative medical causes of the patient’s symptoms, including metabolic, infectious, and hematologic conditions that could produce fatigue, headache, or sensory disturbances. His physician ordered a complete blood count, basic metabolic panel, and urinalysis (Table 4) to assess possible electrolyte abnormalities, systemic infection, or metabolic abnormalities that might contribute to neurologic symptoms. All laboratory results were within normal limits. The available history, physical examination, and limited laboratory evaluation did not identify an alternative explanation, supporting ADS as the most likely diagnosis.

Table 3. Serum laboratory evaluation performed during diagnostic assessment of neurologic symptoms following vilazodone dose reduction.

Table 4. Urinalysis results

Differential Diagnosis. The differential diagnosis included ADS and a relapse of major depressive disorder. Antidepressant discontinuation syndrome was strongly considered given the temporal relationship between the reduction in vilazodone dose and the onset of symptoms, including fatigue, headache, and electric shock-like sensations localized to the head. No features were documented that prompted urgent neurologic workup. Infectious or metabolic etiologies were also considered, as systemic illness can cause fatigue and headaches. However, laboratory evaluation did not reveal evidence of infection, electrolyte disturbance, or metabolic abnormalities. A relapse of major depressive disorder was considered due to the patient’s psychiatric history. Still, the acute onset of distinctive sensory phenomena, including brain zaps, made this explanation less consistent with the clinical presentation.

Diagnosis. Based on the timing of medication dose reduction and the characteristic symptom profile, ADS was considered the most likely diagnosis.

Treatment and management. Management focused on symptomatic relief and careful monitoring while maintaining the current dose of vilazodone to allow for neurochemical stabilization. The patient was advised to use nonsteroidal anti-inflammatory medications as needed for headache. Supportive management was selected since symptoms were not severe enough to require hospitalization or urgent neurologic evaluation, and many discontinuation symptoms resolve spontaneously with time or with stabilization of medication dosing. Continued observation allowed clinicians to monitor symptom progression while avoiding abrupt medication changes that could potentially worsen discontinuation symptoms.

Outcome and follow-up. Two weeks later, while continuing vilazodone 20 mg, the patient reported persistent brain zaps, although they were less frequent. Two weeks thereafter, he reported complete resolution of symptoms. Vilazodone was then fully discontinued. Following discontinuation, the patient experienced a recurrence of brain zaps, notably less intense than during the initial dose reduction. These symptoms resolved spontaneously within 3 weeks of complete cessation of medication.

Case 2

Introductory sentence. A 32-year-old woman presented to primary care with chronic low back pain and depression.

History. A 32-year-old woman with a past medical history of asthma and chronic low back pain secondary to lumbar disc disease and a surgical history of hysterectomy presented for treatment of depression and pain management. She was experiencing situational stress due to an impending residential move. At presentation, her PHQ-9 score was 16 and GAD-7 score was 20, consistent with moderate depression and severe anxiety. She denied any suicidal ideation.

Her medications included cyclobenzaprine 10 mg as needed for back pain and montelukast for asthma. She denied any recreational drug use and reported infrequent alcohol consumption, defined as 1 to 2 drinks less than once every 3 months. She worked as an information technology manager and lived with her husband and 2 children, ages 6 and 9. Her family history was notable for breast cancer in her mother at age 56.

Her primary care provider initiated duloxetine 30 mg daily for combined treatment of depression and chronic pain. At her 8-week follow-up, her PHQ-9 score had improved to 10, and she reported partial symptom relief. Her dose was increased to 60 mg daily. Four months later, her PHQ-9 had decreased to 5 and GAD-7 to 3, indicating remission. The patient had completed her move and felt that the initial stressor had been resolved. She requested to taper off the medication.

Duloxetine was decreased to 30 mg, with instructions to maintain this dose for 2 weeks before further tapering. However, 3 days after the dose reduction, the patient contacted the clinic reporting persistent headaches, "electric zaps" in her brain, dizziness, nausea, and fatigue.

Diagnostic Testing. Diagnostic testing was performed to evaluate possible medical conditions that could produce symptoms like those reported by the patient, including headache, dizziness, fatigue, and sensory disturbances. The patient was evaluated in the clinic, where a physical examination was performed and was unremarkable. Her vital signs were within normal limits, and the neurologic examination revealed no focal deficits, abnormal coordination, or signs of autonomic instability. Her cranial nerves were intact, strength and sensation were normal, and her gait was stable. Laboratory studies included a complete blood count to assess for infection or hematologic abnormalities and a basic metabolic panel to evaluate electrolyte balance and renal function. The physician measured her thyroid-stimulating hormone levels to exclude thyroid dysfunction as a contributor to mood or neurologic symptoms. Since the patient reported systemic symptoms, including fatigue and headache, her physician also performed a rapid influenza diagnostic test to assess for an acute viral illness (Table 5). These results increased the suspicion for ADS following duloxetine dose reduction.

Table 5. Laboratory evaluation performed during diagnostic assessment of neurologic symptoms following duloxetine dose reduction.

Differential diagnosis. The differential diagnosis included ADS, serotonin syndrome, migraine, vestibular disorder, and viral illness. The physician considered serotonin syndrome since the patient was receiving a serotonergic medication. However, the absence of hyperreflexia, clonus, autonomic instability, or altered mental status made this diagnosis unlikely. The physician also considered migraine given the presence of headache and sensory disturbances, but the patient did not report the typical migrainous features of unilateral throbbing pain, photophobia, or aura. Vestibular disorders can produce dizziness and disequilibrium, but they would not typically account for the distinctive electric shock-like sensations described by the patient. The physician also considered viral illness because systemic symptoms, such as fatigue and headache, may accompany viral infections. Laboratory findings and influenza testing were negative, and the timing of symptoms closely followed medication dose reduction.

Diagnosis. Given the characteristic sensory symptoms and the clear temporal association with duloxetine tapering, ADS was determined to be the most likely diagnosis.

Treatment and management. Initial management focused on symptomatic treatment of discontinuation symptoms and close clinical follow-up. The physician prescribed ondansetron 4 mg every 8 hours, as needed, for nausea and acetaminophen 500 mg every 12 hours, as needed, for headache to address the patient’s physical symptoms. These medications were selected because they are commonly used and typically well-tolerated treatments for nausea and headache. Despite supportive therapy, the patient’s symptoms persisted prompting resumption of duloxetine at a lower dose to stabilize serotonergic neurotransmission and allow for a more gradual taper. Duloxetine was restarted at 40 mg daily, lower than her prior 60-mg therapeutic dose but higher than the 30-mg taper dose, and subsequently tapered over 3 months, with dose reductions of approximately 10 mg per month. This slower tapering strategy was selected to reduce the likelihood of recurrent discontinuation symptoms and to allow gradual neurochemical adaptation as the medication dose was decreased.

Outcome and follow-up. Symptoms persisted over the following week, and the patient requested resumption of duloxetine. The physician prescribed 40 mg daily on October 4th, 2024, to allow for a slower taper. The patient reported mild improvement in symptoms but continued to experience “brain zaps” at day 14. The physician then had the patient taper duloxetine over the subsequent 3 months, with 10 mg reductions per month at the beginning and end of November 2024, and the end of December, when it was discontinued. In late February 2025, approximately two months after complete discontinuation, the patient reported near-complete resolution of her symptoms, with brain zaps decreasing in both frequency and severity over approximately 4 weeks from the end of January 2025.

Discussion. We presented 2 illustrative cases of antidepressant discontinuation associated with electric shock-like sensory disturbances, commonly referred to as “brain zaps.” Patients often describe these sensations as abrupt electric shock–like jolts localized to the head, sometimes accompanied by brief disequilibrium, auditory phenomena, or non-electric vibratory sensations.^1-5 The 2 cases presented here highlight brain zaps during dose reduction of 2 different serotonergic agents with distinct pharmacologic profiles, suggesting that this phenomenon may occur across a broader range of antidepressant classes than is commonly appreciated. Brain zap sensations may cause significant distress and contribute to reluctance or difficulty with antidepressant discontinuation.^2,3,5 As such, brain zaps represent a clinically relevant feature of ADS. 

The origin of the term brain zaps remains uncertain, though it appears to have emerged from internet support forums for individuals with antidepressant discontinuation-related sensory disturbances. Around the same time, other terms such as “brain shivers” and “brain flips” also appeared in online forums.¹² It has been proposed that historical misdiagnosis and limited clinical recognition of brain zaps contributed to the development of these forums, which served as an important outlet for patients to share experiences and advocate for broader clinical awareness.¹³ The term's unconventional emergence underscores the potential role of online patient communities as a complementary source of pharmacovigilance data.¹⁴ 

The neurobiological mechanisms underlying brain zaps remain misunderstood. However, recent studies have provided important insights into potential neurobiological contributors. Historically, it was hypothesized that abrupt discontinuation of SSRIs resulted in serotonin receptor down-regulation or a cholinergic rebound.^14,15 SNRIs, such as venlafaxine, act by competitively inhibiting both the serotonin and norepinephrine transporters at presynaptic terminals, thereby reducing neurotransmitter reuptake and increasing extracellular serotonin and norepinephrine concentrations.¹⁶ Vilazodone, an SSRI and 5-HT1A partial agonist, similarly increases serotonergic signaling through serotonin reuptake inhibition and partial activation of pre- and postsynaptic 5-HT receptors.^17,18

One hypothesis is that during chronic SSRI administration, serotonin synthesis and metabolism decrease via indirect activation of 5-HT autoreceptors, thus restoring adaptive neurochemical equilibrium.^14,19-22 Upon abrupt discontinuation, extracellular serotonin levels decline rapidly, disrupting inhibitory feedback mechanisms that had previously compensated for sustained serotonin elevation. It has been proposed that this sudden release of inhibitory feedback leads to increased serotonin synthesis, release, and metabolism, producing heightened neuronal sensitivity.^23,24 In a neural system adapted to chronic serotonin transporter blockade, this transient hyperexcitability of serotonergic neurons and associated downstream neurotransmitter imbalance represents a plausible biological substrate for brain zaps. Fluctuating serotonin levels and altered receptor sensitivity may, in turn, affect norepinephrine, dopamine, gamma-aminobutyric acid, and cholinergic systems.²⁵ These abrupt neurochemical shifts may contribute to sensory disturbances such as paresthesias, dysesthesias, disequilibrium, and brain zaps, although this mechanism remains unproven.^6,24

The cases presented above illustrate several clinically relevant principles regarding brain zaps and discontinuation of serotonergic medications. Consistent with proposed neurobiological models, discontinuation of serotonergic agents may result in a broad constellation of symptoms that can be highly distressing and functionally impairing. Both patients experienced brain zaps, with one case severe enough to interfere with driving. In addition to brain zaps, associated symptoms included headache and fatigue in both cases, with dizziness and nausea reported in Case 2, reflecting the multisystem nature of ADS. Symptomatic treatment with ondansetron and acetaminophen in Case 2 did not alleviate symptoms, suggesting that supportive care alone may be insufficient when neurochemical instability persists. Notably, both patients were receiving higher therapeutic doses at the time of discontinuation. Prior studies involving venlafaxine, paroxetine, duloxetine, and escitalopram demonstrate an association between higher doses, shorter half-life medications, and increased severity of discontinuation symptoms. ^9,10,13 Furthermore, Case 1 suggests symptoms may improve with dose stabilization. Case 2 demonstrates that reinstating or increasing serotonergic medication following symptom emergence can reduce or resolve symptoms, reinforcing the importance of gradual tapering strategies.  

In 2020, approximately 20% of adults in the United States self-reported a lifetime history of depression.²⁶ Given that SSRIs and SNRIs remain first-line pharmacological treatments for depressive disorders, patient education regarding discontinuation phenomena is an essential component of clinical care.²⁷ Clinicians should counsel patients that ADS, including sensory disturbances like “brain zaps,” may occur following dose reduction or cessation of serotonergic medications. Some studies suggest that more severe discontinuation symptoms may be observed among individuals with prolonged antidepressant exposure, those receiving higher doses, or those treated with shorter half-life agents.⁸ Proactive discussion of potential withdrawal symptoms prior to initiating antidepressant therapy may improve long-term adherence and reduce distress during discontinuation. In cases of mild to moderate depressive disorder, evidence-based psychotherapeutic interventions, such as cognitive behavioral therapy and interpersonal therapy, have demonstrated efficacy and should be presented as viable treatment options alongside pharmacological approaches during initial treatment planning.²⁸  

Once therapeutic goals have been achieved with SSRI or SNRI treatment, appropriate tapering protocols are essential to minimize ADS and to prevent unnecessary prolonged medication use driven by fear of withdrawal symptoms.²⁹ Short tapers of 2 to 4 weeks, particularly those involving large weekly dose reductions, have demonstrated minimal benefit over abrupt discontinuation and are generally discouraged.³⁰ Some experts recommend hyperbolic tapering strategies, where doses are reduced in progressively smaller increments as the total dose decreases, as a more effective approach to minimizing discontinuation symptoms.^13,31 This approach is mechanistically consistent with nonlinear serotonin transporter occupancy and gradual neurochemical adaptation. Additional evidence suggests that, in some cases, substitution with fluoxetine, which has a longer half-life, may reduce the severity of discontinuation symptoms when tapering short-half-life SSRIs or SNRIs.³² Although it has been proposed that the temporary addition of another serotonergic agent may mitigate withdrawal symptoms, further research is required to establish the safety, efficacy, and appropriate clinical application of this strategy.

The psychiatric and neurologic literature on brain zaps remains limited at the time of this report. Given that brain zaps may cause significant distress, impair daily functioning, and negatively affect adherence to antidepressant treatment, greater clinical recognition and systematic investigation are warranted. Future research should focus on elucidating the neurobiological mechanisms underlying brain zaps, identifying patient- and medication-related risk factors, and evaluating evidence-based prevention and management strategies. The development of more formal diagnostic descriptors or syndrome classification may facilitate clearer communication between patients and clinicians and support shared decision-making during antidepressant discontinuation. Increased clinical awareness of brain zaps and the use of structured tapering strategies may reduce patient distress, prevent unnecessary diagnostic evaluation, and improve the safety and tolerability of antidepressant discontinuation in routine clinical practice.

AUTHORS
Christina Iverson¹, Jessica Monas, MD², Cole Minsky¹, Conner Monson³, Claudine J. Egol, MD⁴

AFFILIATIONS
¹Alix School of Medicine, Mayo Clinic Arizona, Scottsdale, AZ, USA
²Emergency Department, Mayo Clinic Arizona, Scottsdale, AZ, USA
³Midwestern University School of Medicine, Glendale, AZ, USA
⁴Department of Psychiatry and Psychology, Mayo Clinic Arizona, Scottsdale, AZ, USA

CITATION
Iverson C, Monas J, Minsky C, Monson C, Egol CJ. Brain zaps: a case series on electrical sensations following antidepressant discontinuation. Consultant. Published online. DOI: 10.25270/con.2026.07.000003

DISCLOSURES
The authors declare no conflicts of interest.

CORRESPONDENCE
Claudine Egol, MD, Department of Psychiatry and Psychology, Mayo Clinic Arizona, Scottsdale, AZ, United States (Email: Egol.Claudine@mayo.edu)

References

1. Association AP. Diagnostic and Statistical Manual of Mental Disorders. 5 ed. American Psychiatric Publishing; 2022.
2. Fornaro M, Cattaneo CI, De Berardis D, Ressico FV, Martinotti G, Vieta E. Antidepressant discontinuation syndrome: A state-of-the-art clinical review. Eur Neuropsychopharmacol. 2023;66:1-10. doi:10.1016/j.euroneuro.2022.10.005
3. Warner CH, Bobo W, Warner C, Reid S, Rachal J. Antidepressant discontinuation syndrome. Am Fam Physician. 2006;74(3):449-56.
4. Zajecka J, Tracy KA, Mitchell S. Discontinuation symptoms after treatment with serotonin reuptake inhibitors: a literature review. J Clin Psychiatry. 1997;58(7):291-7. doi:10.4088/jcp.v58n0702
5. Kalfas M, Tsapekos D, Butler M, et al. Incidence and nature of antidepressant discontinuation symptoms: a systematic review and meta-analysis. JAMA Psychiatry. 2025;82(9):896-904. doi:10.1001/jamapsychiatry.2025.1362
6. Blier P, Tremblay P. Physiologic mechanisms underlying the antidepressant discontinuation syndrome. J Clin Psychiatry. 2006;67 Suppl 4:8-13.
7. Fava GA, Benasi G, Lucente M, Offidani E, Cosci F, Guidi J. Withdrawal symptoms after serotonin-noradrenaline reuptake inhibitor discontinuation: systematic review. Psychother Psychosom. 2018;87(4):195-203. doi:10.1159/000491524
8. Gastaldon C, Schoretsanitis G, Arzenton E, et al. Withdrawal syndrome following discontinuation of 28 antidepressants: pharmacovigilance analysis of 31,688 reports from the who spontaneous reporting database. Drug Saf. 2022;45(12):1539-1549. doi:10.1007/s40264-022-01246-4
9. Horowitz MA, Framer A, Hengartner MP, Sorensen A, Taylor D. Estimating risk of antidepressant withdrawal from a review of published data. CNS Drugs. 2023;37(2):143-157. doi:10.1007/s40263-022-00960-y
10. Henssler J, Heinz A, Brandt L, Bschor T. Antidepressant withdrawal and rebound phenomena. Dtsch Arztebl Int. 2019;116(20):355-361. doi:10.3238/arztebl.2019.0355
11. Jiang Y, Qu Y, Du Z, et al. Exploring adverse events of Vilazodone: evidence from the FAERS database. BMC Psychiatry. 2024;24(1):371. doi:10.1186/s12888-024-05813-0
12. Christmas DMB. 'Brain shivers': from chat room to clinic. Psychiatric Bulletin. 2005;29:219-221. doi:10.1192/pb.29.6.219
13. Palmer EG, Sornalingam S, Page L, Cooper M. Withdrawing from SSRI antidepressants: advice for primary care. Br J Gen Pract. 2023;73(728):138-140. doi:10.3399/bjgp23X732273
14. Kurzinger ML, Schuck S, Texier N, et al. Web-based signal detection using medical forums data in france: comparative analysis. J Med Internet Res. 2018;20(11):e10466. doi:10.2196/10466
15. Harvey BH, McEwen BS, Stein DJ. Neurobiology of antidepressant withdrawal: implications for the longitudinal outcome of depression. Biol Psychiatry. 2003;54(10):1105-17. doi:10.1016/s0006-3223(03)00528-6
16. Xue W, Yang F, Wang P, et al. What contributes to serotonin-norepinephrine reuptake inhibitors' dual-targeting mechanism? the key role of transmembrane domain 6 in human serotonin and norepinephrine transporters revealed by molecular dynamics simulation. ACS Chem Neurosci. 2018;9(5):1128-1140. doi:10.1021/acschemneuro.7b00490
17. Plenge P, Yang D, Salomon K, et al. The antidepressant drug vilazodone is an allosteric inhibitor of the serotonin transporter. Nat Commun. 2021;12(1):5063. doi:10.1038/s41467-021-25363-3
18. van Amsterdam C, Seyfried CA. Mechanism of action of the bimodal antidepressant vilazodone: evidence for serotonin1A-receptor-mediated auto-augmentation of extracellular serotonin output. Psychopharmacology (Berl). Jun 2014;231(12):2547-58. doi:10.1007/s00213-013-3428-7
19. Dankoski EC, Carroll S, Wightman RM. Acute selective serotonin reuptake inhibitors regulate the dorsal raphe nucleus causing amplification of terminal serotonin release. J Neurochem. 2016;136(6):1131-1141. doi:10.1111/jnc.13528
20. Fuller RW, Perry KW, Molloy BB. Effect of an uptake inhibitor on serotonin metabolism in rat brain: studies with 3-(p-trifluoromethylphenoxy)-N-methyl-3-phenylpropylamine (Lilly 110140). Life Sci. 1974;15(6):1161-71. doi:10.1016/s0024-3205(74)80012-3
21. Ogren SO, Ross SB, Hall H, Holm AC, Renyi AL. The pharmacology of zimelidine: a 5-HT selective reuptake inhibitor. Acta Psychiatr Scand Suppl. 1981;290:127-51. doi:10.1111/j.1600-0447.1981.tb00715.x
22. Barton CL, Hutson PH. Inhibition of hippocampal 5-HT synthesis by fluoxetine and paroxetine: evidence for the involvement of both 5-HT1A and 5-HT1B/D autoreceptors. Synapse. 1999;31(1):13-9. doi:10.1002/(SICI)1098-2396(199901)31:1
23. Fritze S, Spanagel R, Noori HR. Adaptive dynamics of the 5-HT systems following chronic administration of selective serotonin reuptake inhibitors: a meta-analysis. J Neurochem. 2017;142(5):747-755. doi:10.1111/jnc.14114
24. Collins HM, Gullino LS, Ozdemir D, et al. Rebound activation of 5-HT neurons following SSRI discontinuation. Neuropsychopharmacology. 2024;49(10):1580-1589. doi:10.1038/s41386-024-01857-8
25. Renoir T. Selective serotonin reuptake inhibitor antidepressant treatment discontinuation syndrome: a review of the clinical evidence and the possible mechanisms involved. Front Pharmacol. 2013;4:45. doi:10.3389/fphar.2013.00045
26. Lee B, Wang Y, Carlson SA, et al. National, state-level, and county-level prevalence estimates of adults aged >/=18 years self-reporting a lifetime diagnosis of depression - united states, 2020. MMWR Morb Mortal Wkly Rep. 2023;72(24):644-650. doi:10.15585/mmwr.mm7224a1
27. Chu A, Wadhwa R. Selective Serotonin Reuptake Inhibitors. StatPearls. 2025.
28. Karrouri R, Hammani Z, Benjelloun R, Otheman Y. Major depressive disorder: Validated treatments and future challenges. World J Clin Cases. 2021;9(31):9350-9367. doi:10.12998/wjcc.v9.i31.9350
29. Davies J, Read J. A systematic review into the incidence, severity and duration of antidepressant withdrawal effects: Are guidelines evidence-based? Addict Behav. 2019;97:111-121. doi:10.1016/j.addbeh.2018.08.027
30. Horowitz MA, Taylor D. Tapering of SSRI treatment to mitigate withdrawal symptoms - authors' reply. Lancet Psychiatry. 2019;6(7):562-563. doi:10.1016/S2215-0366(19)30219-6
31. van Os J, Groot PC. Outcomes of hyperbolic tapering of antidepressants. Ther Adv Psychopharmacol. 2023;13:20451253231171518. doi:10.1177/20451253231171518
32. Shapiro B, Cohrs D. Fluoxetine substitution for deprescribing antidepressants: a technical approach. J Psychiatry Neurosci. 2025;50(4):E202-E209. doi:10.1503/jpn.250054

©2026 HMP Global. All Rights Reserved. Any views and opinions expressed are those of the author(s) and/or participants and do not necessarily reflect the views, policy, or position of Consultant360 or HMP Global, their employees, and affiliates.