MOOD

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For many individuals, what appears to be “recurrent depression” reflects an underlying mood spectrum pattern in which cyclicity — not symptom intensity alone — is the defining feature.

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Mixity: Depression With Activation

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Even in the absence of classic DSM hypomania, mixity is often the signal.

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By mixity, I mean depressive states that contain activation:

• Irritability that feels sharp, disproportionate, or out of character

• Inner agitation or motor restlessness

• Crowded, accelerated, or pressured thoughts

• Impulsivity or increased reactivity

• A driven, energized, or dysphoric push — sometimes meeting full hypomanic thresholds, sometimes falling just short

 

What makes it “mixed” is the co-occurrence of depressive symptoms with activation.
Depression with real fire in it.

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The anxiety in these states is not simple rumination. It is physiologic — buzzy, electric, intolerable. It often drives insomnia. It sharpens irritability. It reflects excitatory activation rather than ordinary worry.

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That activated quality is a clinical clue.

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Cyclicity and Antidepressant Destabilization

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When depressions recur at intervals of two years or less, or contain mixed features, I evaluate for instability in excitatory regulatory systems. Glutamatergic signaling governs cortical plasticity and tempo. When poorly regulated, it may accelerate cycling or intensify dysregulation.

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Antidepressants increase excitatory signaling. In some individuals they relieve symptoms briefly. In others they produce no meaningful improvement. In still others they worsen instability — producing dysphoria, agitation, driven insomnia, suicidal activation, mood drop, or shifts toward hypomania. Sometimes lack of response and activation occur simultaneously.

 

Early response itself can be informative. Rapid improvement may reflect accelerated plasticity in excitatory systems. The same acceleration can later underlie loss of effectiveness over time, sometimes called tachyphylaxis or “Prozac poop-out.”

 

When activation emerges — particularly driven insomnia with buzzy anxiety, irritability layered onto depression, or suicidal activation — this represents instability. If there is partial symptom relief in that context, it does not equal stabilization. Antidepressants were designed to lift episodes, not to provide durable prophylaxis. Used chronically without mechanistic clarity, they may perpetuate dysregulation rather than resolve it.

 

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Chronic Depression Still Has Drivers

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Not all individuals cycle. Some present with chronic depression — longstanding low hedonic tone, persistent dysthymia, enduring major depressive episodes, or treatment-resistant unipolar MDD. In my practice, these are rarely uncomplicated first episodes. They are often chronic because underlying drivers were never clarified.

 

Most individuals I evaluate do not fit neatly into a single DSM label. Instead, they present with layered phenotypes:

• Depressive episodes containing agitation or activation

• Physiologic, electric anxiety embedded within low mood

• Periods of increased drive, sharpened focus, or intensified irritability that alter functioning — either within depression or between episodes

• Seasonal or equinox-linked switches

• Postpartum depression or psychosis

• Atypical features — sleeping excessively, increased appetite, heightened rejection sensitivity, or heavy, leaden limb fatigue (like dragging oneself up the stairs)

• Recurrent episodes despite antidepressant trials of adequate dose and duration

• Antidepressant-induced agitation, driven insomnia, mood drop, suicidal ideation, or activation

• Loss of medication effectiveness over time, through tachyphylaxis, or oppositional tolerance

• Chronic, unremitting depression in which biological drivers were never fully assessed

 

These patterns are better understood dimensionally rather than categorically.

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