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Neuroscience: Psychotropics and their influence on the default mode network

Psychotropic medications, designed to alter brain chemistry and treat various mental health disorders, have been found to impact the default mode network both in individuals with neurologic disorders and in healthy volunteers. The default mode network, which is active during rest and involved in self-referential thought and mind-wandering, is altered in many psychiatric conditions. Understanding how psychotropic medications affect the default mode network can provide insights into their mechanisms of action and therapeutic effects.


  • Selective serotonin reuptake inhibitors (SSRIs). In patients with depression, SSRIs have been shown to normalize the heightened activity and connectivity in the default mode network that is typically associated with rumination and negative self-focus. In healthy volunteers, SSRIs can reduce connectivity within the default mode network, which may relate to their anxiolytic effects.
  • Tricyclic antidepressants. Similar to SSRIs, tricyclic antidepressants also affect the default mode network, although their broader pharmacological profile may lead to more complex effects on brain networks.


  • Atypical antipsychotics. Used in schizophrenia and other psychotic disorders, atypical antipsychotics can reduce the hyperconnectivity of the default mode network observed in these conditions. They might also affect the interaction between the default mode network and other networks, such as the salience network, which is important for detecting and responding to important stimuli.
  • In healthy volunteers. The effects of antipsychotics on the default mode network in healthy individuals are less well-studied, but they may disrupt normal default mode network functioning, given their potent neurochemical effects.

Mood Stabilizers

  • Lithium and anticonvulsants. In bipolar disorder, mood stabilizers like lithium and certain anticonvulsants can normalize default mode network connectivity. This may underlie their effectiveness in stabilizing mood and reducing the risk of manic and depressive episodes.


  • Benzodiazepines. Commonly used to treat anxiety disorders, benzodiazepines may decrease default mode network connectivity. This effect could contribute to their anxiolytic and sedative properties. In healthy volunteers, benzodiazepines can induce a general decrease in brain connectivity, including within the default mode network.


  • ADHD medications (eg, methylphenidate, amphetamines). These medications are known to enhance attention and reduce hyperactivity in ADHD by increasing dopamine and norepinephrine levels. They can decrease the excessive default mode network activity often seen in ADHD, potentially improving the balance between task-positive networks and the default mode network.


  • LSD, psilocybin, and MDMA. These substances, while not traditionally considered psychotropic medications in a clinical sense (although this is changing with recent research), have profound effects on the default mode network. They tend to decrease default mode network activity, which may be related to the altered sense of self and the experience of ego dissolution reported by users. Ongoing research into their therapeutic potential (eg, for treatment-resistant depression) is closely examining these effects.

It is important to note that the impact of psychotropic medications on the default mode network can vary widely depending on the specific drug, the dosage, the duration of treatment, and individual differences in brain chemistry and psychiatric conditions. Moreover, the relationship between default mode network changes and clinical outcomes is complex and not fully understood. As research in this area continues to evolve, it will provide a more nuanced understanding of how these medications exert their effects on the brain and how they can be optimally used in treatment.

Related MedLink Neurology content:
Neuroscience: Origins and relevance of the default mode network
Neuroscience: Cataloguing default mode network disruption in neurologic disorders

MedLink acknowledges the use of GPT-4 in drafting this blog entry.

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