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Objective: Use of lithium to augment antidepressant medication has been shown to be beneficial in the acute treatment of depression. The authors examined the efficacy of lithium augmentation in the continuation treatment of unipolar major depressive disorder. Method: Thirty patients with a refractory major depressive episode who had responded to acute lithium augmentation during an open 6-week study participated in a randomized, parallel-group, double-blind, placebo-controlled trial of lithium augmentation during continuation treatment. After a 2-4-week stabilization period following remission, patients were randomly assigned to receive either lithium or placebo for a 4-month period. Antidepressant medication was continued throughout the study. Results: Relapses (including one suicide) occurred in seven (47%) of the 15 patients who received placebo in addition to antidepressants. None (0%) of the 14 patients who received lithium augmentation with antidepressants suffered a relapse during the double-blind phase of the study. Five of the seven relapsing patients in the placebo group developed a depressive episode, and the other two experienced a manic episode. Conclusions: Lithium augmentation in the continuation phase of treatment of unipolar major depressive disorder effectively protects patients against a relapse. Patients who respond to lithium augmentation should be maintained on lithium augmentation for a minimum of 6 months or even longer.

Objective: Regular physical activity is anxiolytic for both healthy subjects and patients with panic disorder. However, the acute antipanic activity of exercise has not yet been studied systematically. Method: The effects of quiet rest or aerobic treadmill exercise (30 minutes at 70% of maximum oxygen consumption) on cholecystokinin tetrapeptide (CCK-4)-induced panic attacks were studied in a crossover design in 15 healthy subjects. The effects were measured with the Acute Panic Inventory. Results: Panic attacks occurred in 12 subjects after rest but in only six subjects after exercise. In both conditions, CCK-4 administration was followed by a significant increase in Acute Panic Inventory scores; however, prior exercise resulted in significantly lower scores than quiet rest. Conclusions: Aerobic exercise has an acute antipanic activity in healthy subjects. If the authors' results are confirmed in patients, the optimum intensity and duration of acute exercise for achieving antipanic effects will have to be characterized.

Objective: Previous studies have shown that neuroactive steroids modulate anxiety and stress reactivity. However, no data on the possible role of these [gamma]-aminobutyric [acid.sub.A] ([GABA.sub.A]) receptor-modulating neuroactive steroids in patients with anxiety disorders are available. Method: The concentrations of 3[alpha],5[alpha]-tetrahydroprogesterone (3[alpha],5[alpha]-THP), 3[alpha],5[beta]-THP, 3[beta],5[alpha]-THP, and their precursors were studied in the plasma of 10 patients with panic disorder and 10 matched healthy comparison subjects. In addition, the effects of paroxetine treatment on neuroactive steroid concentrations were studied in the panic disorder patients over a 24-week period. Results: Unexpectedly, patients with panic disorder had significantly greater concentrations of the positive allosteric modulators 3[alpha],5[alpha]-THP and 3[alpha],5[beta]-THP and significantly lower concentrations of 3[beta],5[alpha]-THP (a functional antagonist for [GABA.sub.A] agonistic steroids), which might result in greater [GABA.sub.A] receptor-mediated neuronal activity. Paroxetine treatment did not affect neuroactive steroid concentrations, which were highly stable over 24 weeks. Conclusions: Differences in neuroactive steroid composition in patients with panic disorder were the opposite of those seen in patients with major depression and may reflect counterregulative mechanisms against the occurrence of spontaneous panic attacks. (Am J Psychiatry 2002; 159:745-747)

Objective: Preclinical evidence exists for the anxiolytic activity of atrial natriuretic peptide, which is released during lactate-induced panic attacks. Atrial natriuretic peptide receptor modulation may have antipanic activity in patients with panic disorder. Method: The effects of 150 [micro]g of atrial natriuretic peptide and placebo on panic attacks induced by cholecystokinin tetrapeptide (CCK-4) (25 [micro]g) were studied in 10 panic disorder patients. The panicogenic activity of CCK-4 was measured with the Acute Panic Inventory. Results: Panic attacks occurred in seven patients in the placebo condition and in two patients in the atrial natriuretic peptide condition. CCK-4 administration was accompanied by a significant increase in Acute Panic Inventory scores. Pretreatment with atrial natriuretic peptide resulted in significantly lower Acute Panic Inventory scores than pretreatment with placebo. Conclusions: The results support the antipanic activity of atrial natriuretic peptide. Nonpeptidergic atrial natriuretic peptide receptor ligands may be ultimately used to treat anxiety disorders. (Am J Psychiatry 2001; 158:1514-1516)