Rumination/Intrusive Thoughts

Rumination is a repetitive, persistent focus on the causes, meanings, and consequences of negative emotions, problems, or events [1]. Common symptoms include:

  • Compulsively thinking about past failures or mistakes
  • Dwelling on sources of distress
  • Overanalyzing problems without active problem-solving

Intrusive thoughts are unwanted, involuntary thoughts or images that interrupt everyday thinking. Symptoms include [2]:

  • Flashbacks to traumatic events
  • Violent, horrific fantasies
  • Taboo thoughts that cause anxiety or disgust
  • Aggressive obsessions

Both rumination and intrusive thoughts are very distressing and difficult to control. They can occur in depression, anxiety, and obsessive disorders.

Ketamine has shown promise for reducing rumination and intrusive thoughts through its effects on neural plasticity. Studies show it rapidly reverses rigid, negative thinking patterns and improves cognitive flexibility [3].

One study found a single ketamine dose significantly reduced rumination in depressed patients within 40 minutes, lasting up to 7 days [4]. Repeated doses may extend benefits.

While limited research exists, ketamine’s ability to rapidly “reset” neural circuits involved in repetitive negative thinking holds promise for treating rumination and intrusive thoughts in multiple psychiatric conditions.

Ketamine therapy has shown promise in rapidly reducing depressive symptoms, and some evidence suggests that it may also help alleviate rumination. Although the exact mechanisms through which ketamine resolves rumination are not fully understood, some of the proposed tools include the following:

  1. NMDA receptor antagonism: Ketamine is known to block NMDA (N-methyl-D-aspartate) receptors in the brain, which may contribute to its rapid antidepressant effects and potentially reduce rumination by altering glutamatergic neurotransmission.
  2. Synaptogenesis: Ketamine may promote synaptogenesis, forming new connections between neurons, which can help improve mood and cognitive flexibility, thus reducing rumination.
  3. Neurotrophic factors: Ketamine might increase the release of neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), essential for neuronal survival, growth, and synaptic plasticity, potentially improving the brain’s capacity for adaptive thinking and reducing rumination.
  4. Functional connectivity: Ketamine has been shown to alter functional connectivity in brain networks associated with self-referential thinking and emotion regulation, which could potentially help reduce rumination.
  5. Default Mode Network (DMN): The DMN is a network of brain regions active when a person is not focused on the outside world and is engaged in self-referential thinking or mind-wandering. Research has shown that DMN is hyperactive in individuals with depression and rumination. Ketamine has been found to reduce DMN connectivity, which could help alleviate rumination rapidly.

Rapid antidepressant effects: The fast-acting nature of ketamine therapy could immediately reduce depressive symptoms, potentially breaking the cycle of rumination more quickly than traditional antidepressants.

It is crucial to emphasize that ketamine therapy should be administered under the supervision of healthcare professionals experienced in its use, as the long-term effects on rumination are not yet fully understood. Further research is needed to determine how ketamine therapy resolves rumination and optimize its use.


[1] Nolen-Hoeksema, S. (1991). Responses to depression and their effects on the duration of depressive episodes. Journal of Abnormal Psychology, 100(4), 569–582.

[2] Clark DA, Rhyno S. Unwanted intrusive thoughts in nonclinical individuals: Implications for clinical disorders. In: Clark DA, editor. Intrusive Thoughts in Clinical Disorders: Theory, Research, and Treatment. New York: Guilford Press; 2005. p. 1–29.

[3] Abdallah CG, Sanacora G, Duman RS, Krystal JH. Ketamine and rapid-acting antidepressants: a window into a new neurobiology for mood disorder therapeutics. Annu Rev Med. 2015;66:509-523. doi: 10.1146/annurev-med-053013-062946.

[4] Perkins AM, Ettinger U, Williams SCR, Reilly JL,oney PA. Effects of Ketamine on Encoding and Retrieval of Episodic Memory in Relation to Psychotic-Like Symptoms. J Psychopharmacol. 2018;32(6):621-633. doi:10.1177/0269881118767497

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