Depression is not one condition. The word describes a clinical syndrome, a cluster of symptoms that can arise from different biological mechanisms, in different neurological contexts, with different patterns of treatment response. This is the explanation, not the excuse, for why antidepressant medications work well for some patients and do not work at all for others. The medication is not failing because the patient is not taking it correctly, or not trying hard enough, or not giving it adequate time. It is failing because the depression in that patient is being driven by mechanisms that the medication does not adequately address.
Dr. Thomas Hughes at NeoPsych in Los Angeles works with patients who have been through this experience. They have tried one medication, then another, then a combination. They have experienced side effects that were sometimes worse than the depression itself. They have been told that their dose needs to be higher, or that they need to add another medication, or that they should be patient and wait longer for a response that never fully arrived. For these patients, transcranial magnetic stimulation therapy represents a fundamentally different approach, one that addresses the neurobiology of depression directly rather than through the intermediary of systemic pharmacology.
Why Antidepressants Fail a Significant Minority of Patients
Antidepressant medications work primarily by modulating neurotransmitter systems in the brain. Selective serotonin reuptake inhibitors increase the availability of serotonin in synapses. Serotonin-norepinephrine reuptake inhibitors affect both serotonin and norepinephrine systems. Bupropion primarily affects dopamine and norepinephrine. These mechanisms are well established and benefit many patients. But they do not address all of the neurobiological factors that contribute to depression.
The neuroscience of depression involves not just neurotransmitter levels but also the functional connectivity between brain regions, the structural integrity of neural circuits that regulate mood and emotion, patterns of cortical activity that become entrenched in depressive states, and the inflammatory and metabolic processes that influence neurological function. Medications that adjust neurotransmitter levels at the synapse do not directly address these circuit-level and structural abnormalities.
Antidepressants may produce partial improvement, or no improvement at all, regardless of the dose or the duration of treatment. This is not treatment failure in the sense of inadequate medication management. It is a mismatch between the intervention and the underlying pathophysiology.
What TMS Does That Antidepressants Cannot
Transcranial magnetic stimulation is a non-invasive brain stimulation therapy that uses focused magnetic pulses to directly modulate the activity of specific cortical regions. The primary target for depression treatment is the dorsolateral prefrontal cortex, a region of the frontal brain that shows reduced activity and impaired connectivity in patients with depression.
The dorsolateral prefrontal cortex is involved in executive function, emotional regulation, and the modulation of the limbic system, including the amygdala, which is responsible for generating emotional responses, including fear and sadness. When the dorsolateral prefrontal cortex is underactive, its capacity to regulate limbic activity is reduced, and the emotional hyperreactivity and persistent negative affect characteristic of depression are less effectively controlled.
TMS therapy applies repetitive magnetic pulses to the dorsolateral prefrontal cortex at a frequency that increases cortical excitability in this underactive region. Over the course of treatment, this stimulation produces neuroplastic changes, strengthening the synaptic connections in the target region and improving its functional connectivity with downstream structures. This is how TMS produces lasting antidepressant effects rather than transient symptomatic relief.
The mechanism is direct. It does not work through the bloodstream. It does not require hepatic metabolism. It does not interact with other medications in the ways that antidepressants often do. And it does not produce the systemic side effects, including weight gain, sexual dysfunction, sedation, and emotional blunting, that cause a significant proportion of antidepressant patients to discontinue their medication.
What Treatment Looks Like at NeoPsych
Dr. Thomas Hughes at NeoPsych begins with a comprehensive psychiatric evaluation to confirm the diagnosis, review the patient’s treatment history, assess appropriateness for TMS, and identify any contraindications. Patients with metallic implants near the head, a history of seizures, or certain other medical conditions are not appropriate candidates for TMS, and this screening is conducted carefully.
The standard TMS protocol for depression at NeoPsych consists of daily treatment sessions, Monday through Friday, for approximately six weeks, totaling 30 to 36 sessions. Each session is performed in a comfortable treatment chair. The TMS device is positioned over the scalp at the treatment site. Patients hear clicking sounds and feel a tapping sensation during stimulation. No anesthesia or sedation is required. Sessions last between 20 and 40 minutes, depending on the protocol.
NeoPsych also offers theta burst stimulation, an FDA-cleared TMS protocol that delivers equivalent therapeutic stimulation in approximately three minutes per session, and accelerated TMS protocols for patients who need a more rapid response.
After each session, patients leave the clinic and return to normal activities, including driving and work. There are no restrictions during the treatment period.
Who Responds to TMS
Approximately 50 to 60 percent of patients with treatment-resistant depression experience significant improvement with TMS, and approximately 30 to 35 percent achieve full remission. These numbers are particularly meaningful in the context of treatment-resistant depression, where prior medication trials have failed to provide adequate relief.
Patients who are most likely to respond include those with major depressive disorder who have not achieved adequate response to one or more antidepressant medications, those who cannot tolerate antidepressant side effects, and those who have not achieved full remission with medication alone and want to address the residual symptoms that significantly impair their quality of life.
If you are in Los Angeles and have not found adequate relief through medication, contact NeoPsych to schedule a TMS evaluation with Dr. Thomas Hughes.